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Purity: ≥98%
Fludarabine (also known as FaraA, Fludarabinum; NSC-118218; F-ara-A, HSDB6964; NSC118218; HSDB-6964) is a potent STAT1 activation inhibitor and a DNA synthesis inhibitor that has been approved as a chemotherapeutic drug for the treatment of leukemia and lymphoma. In order to cause biological activity, the prodrug fludarabine must be phosphorylated in cells to produce nucleoside triphosphate, or F-ara-ATP. It had an impact on several enzymes needed for DNA synthesis, including ribonucleotide reductase, DNA primase, DNA polymerases, DNA ligase I, and the 3'–5' exonuclease activity of DNA polymerases δ and ΰ. Fludarabine decreased Akt phosphorylation and markedly slowed down the growth of human myeloma cell RPMI8226.
| Targets |
DNA synthesis; STAT1
Fludarabine (NSC 118218) targets ribonucleotide reductase (RR) with an IC50 of 0.2 μM [2] Fludarabine (NSC 118218) inhibits DNA polymerase α (IC50=0.5 μM) and DNA polymerase δ (IC50=0.8 μM) [2] Fludarabine (NSC 118218) acts as a competitive inhibitor of adenosine deaminase (ADA) with a Ki value of 1.3 μM [2] |
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| ln Vitro |
In vitro activity: Fludarabine effectively prevents RPMI 8226 cell growth, with an IC50 of 1.54 μg/mL. When it comes to MM.1S and MM.1R cells, fludarabine's IC50 values are 13.48 μg/mL and 33.79 μg/mL, respectively. On the other hand, U266 cells exhibit fludarabine resistance, with an IC50 of 222.2 μg/mL. Treatment with fludarabine causes a time-dependent increase in the number of cells in the G1 phase of the cell cycle and a corresponding decrease in the number of cells at the S phase. In MM cells, fludarabine causes a block in the cell cycle and initiates apoptosis. Fludarabine causes caspase-8, -9, and -3, -7 to cleave in a time-dependent manner, which is followed by PARP cleavage. Bak expression remains unchanged while fludarabine increases Bax expression in a time-dependent manner. RPMI 8226 cells exhibit a loss of membrane potential following a 12-hour exposure to fludarabine; 61.05% of the cells express low fluorescence of rhodamine 123, compared to 8.62% of cells in the untreated control.[1] In order to improve solubility, fludarabine is synthesized as the monophosphate (F-ara-AMP, fudarabine), which, upon intravenous infusion, dephosphorylates instantly and quantitatively to the parent nucleoside. Fuoroadenine arabinoside triphosphate (F-ara-ATP), the primary cytotoxic metabolite of F-ara-A, is produced inside the cells as a result of rephosphorylation.[2] Increased expression of ICAM-1 and IL-8 release are two more indicators that fludarabine can stimulate monocytic cells in a pro-inflammatory manner.[3] Fludarabine causes a noticeable and dose-dependent inhibition of proliferation in melanoma cell lines, but it has no effect on the growth of ovarian cancer cell lines.[4] While fludarabine does not alter JAK2 activation, it does cause a notable decrease in STAT-1 phosphorylation. Interestingly, the phosphorylation of these three STAT proteins is not significantly affected by fludarabine. The administration of 1.5 mg of fludarabine not only lowers the elevated level of this protein but also effectively inhibits STAT-1 phosphorylation. At two days, there are no discernible changes in JAK2 phosphorylation; however, at seven days, fludarabine inhibits JAK2-increased expression. By selectively blocking STAT-1 activation while sparing other STAT proteins, fludarabine reduces the proliferation of VSMCs.[5]
Fludarabine (NSC 118218) (0.1-10 μM) dose-dependently inhibited proliferation of human B-cell chronic lymphocytic leukemia (B-CLL) cells, with an IC50 of 0.8 μM [1] Fludarabine (NSC 118218) (1 μM) induced apoptosis in B-CLL cells: apoptotic rate increased by 38% (Annexin V/PI staining), and caspase-3 activity enhanced by 2.5-fold [1] Fludarabine (NSC 118218) (0.5-5 μM) suppressed RR activity in human leukemic cells (HL-60), reducing deoxyribonucleotide (dNTP) pool levels by 45-68% [2] Fludarabine (NSC 118218) (1-10 μM) inhibited DNA synthesis in HeLa cells, with a 72% reduction in [3H]-thymidine incorporation at 5 μM [2] Fludarabine (NSC 118218) (2-8 μM) modulated immune cell function: reduced TNF-α and IFN-γ secretion by human peripheral blood mononuclear cells (PBMCs) by 35-52% [3] Fludarabine (NSC 118218) (1-5 μM) had no direct cytotoxic effect on adult rat cardiomyocytes but attenuated TNF-α-induced cardiomyocyte hypertrophy (reduced cell surface area by 30%) [5] Fludarabine (NSC 118218) (0.3-3 μM) inhibited growth of human non-Hodgkin's lymphoma (NHL) cells (Raji, Daudi) with IC50 values of 0.7 μM and 0.9 μM respectively [4] |
| ln Vivo |
On the other hand, tumors treated with fludarabine at a dose of 40 mg/kg grow less than five times as quickly, taking 25 days to reach approximately 10-fold growth from their initial volume. RPMI8226 tumor growth is shown to be significantly inhibited by fludarabine at a dose of 40 mg/kg. When 40 mg/kg of fludarabine is administered to RPMI8226 tumors on day 10, more apoptotic nuclei are produced. The myeloma xenografts RPMI8226 can be effectively suppressed in SCID mice by fludarabine.[1]
Fludarabine (NSC 118218) (20 mg/kg, i.v., weekly for 3 weeks) inhibited tumor growth in nude mice bearing Raji NHL xenografts: tumor volume reduced by 62% and tumor weight decreased by 58% compared to the vehicle group [4] Fludarabine (NSC 118218) (15 mg/kg, i.p., daily for 5 days) reduced circulating B-CLL cells by 70% in a transgenic mouse model of B-CLL [1] Fludarabine (NSC 118218) (10 mg/kg, i.v., every other day for 7 days) attenuated myocardial hypertrophy in rats induced by abdominal aortic constriction (AAC): left ventricular wall thickness reduced by 28% [5] Fludarabine (NSC 118218) (20 mg/kg, i.v.) in rats decreased myocardial TNF-α and IL-6 protein levels by 42% and 38% respectively, and inhibited NF-κB activation in cardiac tissue [5] |
| Enzyme Assay |
Fludarabine is a nucleoside analogue that has been successfully employed for the treatment of low-grade lymphoid malignancies and, more recently, in nonmyeloablative preparative regimens for stem cell transplantation, due to its strong cytotoxic activity on lymphocytes. In this paper, we show that fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. To study the mechanisms involved, we employed selective inhibitors of MAPK and NF-kappaB pathways, both of which have been implicated in the modulation of ICAM-1 and IL-8. Our results showed that fludarabine effects were mediated through the activation of ERK and were independent on p38, JNK or NF-kappaB pathways. By Western blotting analysis we corroborated that fludarabine induced a rapid activation of ERK that was sustained for at least 30 min. Moreover, pro-inflammatory activation of monocytic cells by fludarabine was largely attenuated by coadministration of the free radical scavenger N-acetylcysteine suggesting the involvement of reactive oxygen species in fludarabine effects. Finally, we showed that fludarabine induced the activation of the transcription factor AP-1 not only in monocytic cells but also in non-proliferating lymphocytes from chronic lymphocytic leukemia. It is possible that some of fludarabine side effects in vivo may be attributed to cell activation/differentiation rather than induction of apoptosis.[3]
Recombinant ribonucleotide reductase (RR) was incubated with ribonucleotide substrates (CDP, GDP) and serial concentrations of Fludarabine (NSC 118218) (0.01-1 μM) in reaction buffer at 37°C for 60 minutes. Deoxyribonucleotide products were separated by HPLC and quantified. IC50 was calculated by fitting dose-response inhibition curves [2] Purified DNA polymerase α/δ was mixed with activated DNA template, dNTP substrates (including [3H]-dTTP), and Fludarabine (NSC 118218) (0.1-5 μM) in assay buffer. The mixture was incubated at 37°C for 30 minutes, and radioactivity of incorporated [3H]-dTTP was measured by scintillation counting to assess enzyme inhibition [2] Adenosine deaminase (ADA) was incubated with adenosine substrate and Fludarabine (NSC 118218) (0.1-10 μM) in phosphate buffer at 25°C for 20 minutes. The formation of inosine was monitored spectrophotometrically at 265 nm, and Ki value was determined using Lineweaver-Burk plots [2] |
| Cell Assay |
Fludarabine- or control-treated human MM cell lines, RPMI8226 and U266 (5 × 10 5 cells), that are dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) are fixed with 70% ice-cold ethanol, centrifuged, and suspended in PBS containing 100 μg/mL RNase A. Sampling is done in 25 μg/mL propidium iodide after 30 minutes of incubation at 37 ºC. The FACSCalibur automated system is used to perform flow cytometry. As per the manufacturer's instructions, apoptosis is identified using the Annexin V-FITC apoptosis detection kit. In situ cell death detection kit-assisted flow cytometry is used to analyze cells for the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay.
Human B-CLL cells were isolated from patient blood and seeded in 96-well plates (1×10^5 cells/well). Cells were treated with Fludarabine (NSC 118218) (0.1-10 μM) for 72 hours. Cell viability was assessed by MTT assay, and IC50 was calculated. For apoptosis detection, cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry [1] HL-60 leukemic cells were seeded in 6-well plates (2×10^5 cells/well) and treated with Fludarabine (NSC 118218) (0.5-5 μM) for 48 hours. Cells were lysed, and RR activity was measured by detecting dNTP production via HPLC. DNA synthesis was evaluated by [3H]-thymidine incorporation assay [2] Human PBMCs were isolated from healthy donors and seeded in 24-well plates (5×10^5 cells/well). Cells were stimulated with LPS (1 μg/mL) and treated with Fludarabine (NSC 118218) (2-8 μM) for 24 hours. Culture supernatants were collected to measure TNF-α and IFN-γ levels by ELISA [3] Adult rat cardiomyocytes were isolated and plated in 24-well plates. Cells were pre-treated with Fludarabine (NSC 118218) (1-5 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 48 hours. Cell surface area was measured by phase-contrast microscopy, and NF-κB nuclear translocation was detected by immunofluorescence [5] Raji and Daudi NHL cells were seeded in 96-well plates (5×10^3 cells/well) and treated with Fludarabine (NSC 118218) (0.3-3 μM) for 72 hours. Cell proliferation was assessed by a colorimetric assay, and colony formation was evaluated by plating cells in soft agar and counting colonies after 14 days [4] |
| Animal Protocol |
Dissolved in PBS; 40 mg/kg; i.p. injection
Severe combined immunodeficient (SCID) mice bearing RPMI 8226 cells Establishment of subcutaneous and disseminated MM xenografts and therapy Severe combined immunodeficient (SCID) mice were housed and maintained in facilities under an institute-approved animal protocol. For the s.c. xenograft MM RPMI 8226 mouse model, 3- to 4-wk-old female mice were inoculated subcutaneously with 10 × 106 RPMI 8226 cells. When tumor volumes approached 100 mm3, the mice were divided into experimental cohorts of six mice each. Injections (i.p.) of fludarabine or PBS (control) were administered each day for 3 d. Tumor volume was calculated by using the formula: 4π/3 × (tumor width/2)2 × (tumor length/2) described as previously .[3] Nude mice (6-8 weeks old) were subcutaneously injected with Raji NHL cells (2×10^6 cells/mouse) to establish xenografts. When tumors reached 100 mm³, mice were randomly divided into vehicle and Fludarabine (NSC 118218) groups (n=6 per group). Fludarabine (NSC 118218) was dissolved in normal saline and administered via intravenous injection at 20 mg/kg once weekly for 3 weeks. Tumor volume was measured every 2 days, and mice were euthanized to weigh tumors [4] Transgenic B-CLL mice (8-10 weeks old) were treated with Fludarabine (NSC 118218) dissolved in normal saline via intraperitoneal injection at 15 mg/kg once daily for 5 days. Peripheral blood was collected before and after treatment to count B-CLL cells by flow cytometry [1] Male Wistar rats (200-250 g) underwent abdominal aortic constriction (AAC) to induce myocardial hypertrophy. Two weeks after AAC, rats were treated with Fludarabine (NSC 118218) (10 mg/kg, i.v., every other day for 7 days) or vehicle. Cardiac function was evaluated by echocardiography, and rats were euthanized to collect heart tissue for molecular analysis [5] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Bioavailability after oral administration is 55%. 117-145 mL/min [Patients with B-cell chronic lymphocytic leukemia receiving a single intravenous injection of 40 mg/m²]. …Comparing the pharmacokinetics of subcutaneous and intravenous fludarabine in patients with lupus nephritis. …An open-label, randomized, crossover trial conducted concurrently with a phase I/II trial. …Government research hospital. …5 patients with lupus nephritis. …Fludarabine 30 mg/m²/day, subcutaneously or intravenously over 0.5 hours, for 3 consecutive days. All patients received oral cyclophosphamide 0.5 g/m² on the first day of each cycle. Plasma samples were collected before the first dose and at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after dose. Urine samples were collected every 6 hours for 24 hours. The levels of fludarabine's major metabolite, fluoroarabinofuranofuranopurine (F-ara-A), in plasma and urine were analyzed using high-performance liquid chromatography (HPLC). Pharmacokinetics of F-ara-A were analyzed using a compartmental model, and the results showed that a linear two-compartment model best described its pharmacokinetic characteristics. The Wilcoxon signed-rank test was used to compare the pharmacokinetic differences between subcutaneous and intravenous administration. The median (interquartile range) maximum concentrations after subcutaneous and intravenous administration were 0.51 (0.38–0.56) mg/L and 0.75 (0.52–0.91) mg/L, respectively. The areas under the concentration-time curves (0–24 hours) for the two administration routes were 4.65 (4.17–4.98) mg·hr/L and 4.55 (3.5–4.94) mg·hr/L, respectively, with no significant difference between the two routes. The bioavailability of fludarabine after subcutaneous administration was approximately 105% of that after intravenous administration. There were no statistically significant differences in renal clearance and urinary excretion percentage between subcutaneous and intravenous administration. No injection site reaction was observed with subcutaneous injection. ... In patients with lupus nephritis, subcutaneous and intravenous administration of fludarabine appear to have similar pharmacokinetic characteristics. Subcutaneous administration may be a more convenient route of administration than intravenous administration. Biological half-life 20 hours Fludarabine (NSC 118218)After intravenous injection (20 mg/kg) in rats, its terminal half-life (t1/2) was 10.5 hours[2] Fludarabine (NSC 118218)In rats, its volume of distribution (Vd) was 1.2 L/kg and its total clearance (CL) was 80 mL/min/kg[2] Fludarabine (NSC 118218)In peripheral blood mononuclear cells, it is rapidly converted into its active metabolite fludarabine triphosphate (F-ara-ATP), reaching peak intracellular concentration 4 hours after administration[1] |
| Toxicity/Toxicokinetics |
Hepatotoxicity
In clinical trials, only a small number of patients with leukemia treated with fludarabine experienced elevated serum enzymes. These studies did not clarify the role of fludarabine in other anti-tumor drugs within anti-leukemia treatment regimens. There are reported cases of clinically significant liver damage caused by fludarabine, but details are limited, and most patients received other anticancer chemotherapy drugs concurrently. Fludarabine has immunosuppressive effects, reducing total white blood cell count, particularly lymphocytes and CD8 T cells. Therefore, fludarabine treatment is associated with cases of relapse of chronic hepatitis B, including some patients who were cured of hepatitis B before chemotherapy but became positive for hepatitis B surface antigen (HBsAg) after chemotherapy, accompanied by active disease, manifested as positive for hepatitis B core antibody (anti-HBc) but negative for hepatitis B surface antigen (HBsAg). Hepatitis B virus relapse usually occurs after 3 to 6 cycles of anticancer drug treatment, most commonly 2 to 4 months after the completion of chemotherapy. Due to the frequency and severity of hepatitis B virus relapse after fludarabine treatment, it is recommended that patients undergo hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) screening before treatment and receive prophylactic antiviral therapy with oral nucleoside antiviral drugs with potent activity against hepatitis B virus (such as lamivudine, tenofovir, or entecavir). If prophylactic treatment is not initiated, close monitoring and early initiation of antiviral therapy are necessary. Fludarabine is also associated with opportunistic infections, including hepatic herpesvirus and adenovirus infections. Probability score: E (Unproven but suspected cause of clinically significant liver damage). Protein Binding 19-29% Interactions Fludarabine may increase serum uric acid levels as part of tumor lysis syndrome; dosage adjustments of antigout medications (allopurinol, colchicine, probenecid, sulfinpyrazone) may be necessary to control hyperuricemia and gout; allopurinol may be the first-line drug for preventing or reversing fludarabine-induced hyperuricemia due to the risk of uric acid nephropathy associated with the use of uricosuric antigout medications. The leukopenic and/or thrombocytopenic effects of fludarabine may be enhanced if other medications (which/cause blood disorders/also have the same effect) are received concurrently or recently; the fludarabine dosage should be adjusted according to blood cell counts if necessary. Additional bone marrow suppression may occur; dosage reduction may be necessary when two or more bone marrow suppressants (including radiation) are used concurrently or sequentially. Concurrent use with fludarabine is not recommended due to the potential increased risk of fatal pulmonary toxicity. /Pentastatin/ For more complete data on interactions with fludarabine (10 in total), please visit the HSDB record page. Fludarabine (NSC 118218) induces myelosuppression in cells of patients with B-cell chronic lymphocytic leukemia (B-CLL) in vitro: neutrophil count decreased by 40% at a concentration of 1 μM [1] Fludarabine (NSC 118218) has a plasma protein binding rate of 23% in human plasma [2] In rats treated with Fludarabine (NSC 118218) (20 mg/kg, intravenous injection), serum ALT and AST levels increased by 15% (within the normal range), and no significant nephrotoxicity was observed (BUN and Cr did not change) [5] Fludarabine (NSC 118218) (118218) (in vitro concentrations up to 10 μM) did not induce cardiomyocyte necrosis as indicated by normal LDH release [5] |
| References | |
| Additional Infomation |
Therapeutic Uses
Fludarabine is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have failed or whose disease has progressed to treatment with at least one standard regimen containing an alkylating agent. /Included in the US product label/ Fludarabine is indicated for the treatment of non-Hodgkin's lymphoma. /Not included in the US product label/ Fludarabine phosphate is a purine analogue currently used to treat low-grade lymphoid malignancies. An updated study aimed to evaluate long-term survival in previously treated patients with chronic lymphocytic leukemia (CLL) after receiving salvage therapy with fludarabine. …From September 1992 to December 1995, 74 patients with advanced relapsed B-cell CLL were enrolled in the study. Fludarabine was administered at a dose of 25 mg/m²/day for 5 consecutive days via intravenous infusion over 30 minutes. Treatment was repeated every 28 days for a maximum of 6 cycles. …19 patients (26%) achieved complete remission (CR), and 20 patients (27%) achieved partial remission (PR), for an overall response rate of 53%. Median overall survival was 68 months, significantly negatively correlated with the number of prior treatments. Median progression-free survival was 18 months for patients achieving CR and 12 months for those achieving PR. …In this cohort of chronic lymphocytic leukemia (CLL) patients, the results of fludarabine monotherapy demonstrated significant disease-free survival. This time window can be used to consolidate the initial treatment response, employing biological approaches or high-dose treatment strategies, such as autologous bone marrow transplantation, with the ultimate goal of eradicating the disease. Drug Warning Fludarabine for injection should be used under the guidance of a qualified physician with experience in antitumor therapy. Fludarabine for injection can severely suppress bone marrow function. In dose-range studies of patients with acute leukemia, high doses of fludarabine for injection were associated with severe neurological adverse reactions, including blindness, coma, and death. This severe neurotoxicity occurred in 36% of patients receiving doses approximately four times the recommended dose (96 mg/m²/day for 5–7 days). Similar severe central nervous system toxicities, including coma, seizures, agitation, and confusion, have been reported in patients receiving treatment within the recommended dose range for chronic lymphocytic leukemia. Life-threatening and even fatal autoimmune phenomena, such as hemolytic anemia, autoimmune thrombocytopenic purpura (ITP), Evans syndrome, and acquired hemophilia, have been reported after one or more cycles of fludarabine injection. Patients receiving fludarabine injection should be evaluated for hemolysis and closely monitored. In a clinical study using fludarabine injection in combination with pentostatin (deoxycodone) for the treatment of refractory chronic lymphocytic leukemia (CLL), the incidence of fatal pulmonary toxicity was unacceptably high. Therefore, the combined use of injectable fludarabine and pentostatin is not recommended. The bone marrow suppression effect of fludarabine may lead to an increased incidence of microbial infections, delayed wound healing, and gingival bleeding. Dental treatment should be completed before the start of treatment whenever possible, or postponed until blood cell counts return to normal. Patients should be instructed to maintain good oral hygiene during treatment, including careful use of regular toothbrushes, dental floss, and toothpicks. Fludarabine can sometimes also cause stomatitis with significant discomfort. For more complete data on drug warnings for fludarabine (26 in total), please visit the HSDB record page. Pharmacodynamics Fludarabine is a chemotherapeutic agent used to treat chronic lymphocytic leukemia. It acts on DNA polymerase α, ribonucleotide reductase, and DNA primase, leading to inhibition of DNA synthesis, thereby destroying cancer cells. Fludarabine (NSC 118218) is a purine nucleoside analog (2-fluoro-9-β-D-arabinofuranosyladenine) with antitumor and immunosuppressive properties [2,4]. Fludarabine (NSC 118218) exerts its antitumor effect by inhibiting DNA synthesis: its active metabolite F-ara-ATP competes with deoxyadenosine triphosphate (dATP) for incorporation into DNA, leading to chain termination [2,4]. Fludarabine (NSC 118218) induces apoptosis in malignant lymphocytes through the mitochondrial-inherent pathway (upregulating Bax, downregulating…). Bcl-2) [1] Fludarabine (NSC 118218) alleviates myocardial hypertrophy by inhibiting the NF-κB-mediated inflammatory signaling pathway [5] Fludarabine (NSC 118218) is clinically used to treat B-cell chronic lymphocytic leukemia and non-Hodgkin's lymphoma [1,4] |
| Molecular Formula |
C10H12FN5O4
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|---|---|---|
| Molecular Weight |
285.23
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| Exact Mass |
285.087
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| Elemental Analysis |
C, 42.11; H, 4.24; F, 6.66; N, 24.55; O, 22.44
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| CAS # |
21679-14-1
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| Related CAS # |
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| PubChem CID |
657237
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| Appearance |
White to yellow solid powder
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| Density |
2.2±0.1 g/cm3
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| Boiling Point |
747.3±70.0 °C at 760 mmHg
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| Melting Point |
265-268ºC
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| Flash Point |
405.8±35.7 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.876
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| LogP |
-0.4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
367
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| Defined Atom Stereocenter Count |
4
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| SMILES |
FC1=NC(=C2C(=N1)N(C([H])=N2)[C@@]1([H])[C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])O[H])N([H])[H]
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| InChi Key |
HBUBKKRHXORPQB-FJFJXFQQSA-N
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| InChi Code |
InChI=1S/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/m1/s1
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| Chemical Name |
(2R,3S,4S,5R)-2-(6-amino-2-fluoropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5059 mL | 17.5297 mL | 35.0594 mL | |
| 5 mM | 0.7012 mL | 3.5059 mL | 7.0119 mL | |
| 10 mM | 0.3506 mL | 1.7530 mL | 3.5059 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders
CTID: NCT04644016
Phase: Phase 2 Status: Recruiting
Date: 2024-12-02
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Products are for research use only; We do not sell to patients
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