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| 50mg |
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Purity: ≥98%
Topotecan HCl (formerly known as NSC609699, Nogitecan, NSC-609699, SKFS-104864A; trade name: Hycamtin), an FDA approved drug for cancer treatment, is a topoisomerase I inhibitor with potent antineoplastic activity. In cell-free assays, it inhibits topoisomerase I in MCF-7 Luc and DU-145 Luc cells with IC50 values of 13 nM and 2 nM, respectively. A semisynthetic derivative of camptothecin with antitumor properties is topotecan. Topotecan selectively stabilizes topoisomerase I-DNA covalent complexes during the S phase of the cell cycle. This prevents topoisomerase I-mediated single-strand DNA breaks from religating and creates potentially fatal double-strand DNA breaks when the DNA replication machinery comes into contact with the complexes.
| Targets |
Topo I (DU-145 Luc cells) ( IC50 = 2 nM ); Topo I (MCF-7 Luc cells) ( IC50 = 13 nM )
Topotecan HCl (SKF 104864A) targets DNA topoisomerase I (Topo I) with an IC50 of 0.2 μM for inhibiting enzyme-mediated DNA relaxation and stabilizing Topo I-DNA cleavage complexes [2] |
|---|---|
| ln Vitro |
In vitro activity: Topotecan is observed to have stronger drug activity for MCF-7 Luc and DU-145 Luc cells. [1] By stabilizing the covalent complex between topoisomerase I and DNA and inhibiting the religation of enzyme-linked single-strand DNA breaks, topotecan causes cytotoxicity during DNA replication. In radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, topotecan stabilizes topoisomerase I/DNA cleavable complexes, induces rapid apoptotic cell death despite high-level expression of bcl-2 protein, and dose-dependently suppresses the clonogenic growth of ALL cells. [2]
Topotecan HCl (SKF 104864A) (0.05-5 μM) dose-dependently inhibited proliferation of human ovarian cancer cells (A2780, OVCAR3) with IC50 values of 0.4 μM and 0.6 μM respectively [1] Topotecan HCl (SKF 104864A) (0.3 μM) induced apoptosis in HL-60 human leukemia cells: apoptotic rate increased by 52% (Annexin V/PI staining), caspase-3 activity enhanced by 3.6-fold, and DNA single-strand breaks (γ-H2AX foci) increased by 4.0-fold [2] Topotecan HCl (SKF 104864A) (0.2-2 μM) suppressed colony formation of human glioma cells (U87, U251) by 60-78% after 14 days of culture [3] Topotecan HCl (SKF 104864A) (0.5 μM) caused S phase cell cycle arrest in A2780 cells, with S phase population increased from 30% (control) to 65% [1] Topotecan HCl (SKF 104864A) (0.1-1 μM) inhibited Topo I activity in a cell-free system, reducing DNA relaxation efficiency by 55-92% [2] Topotecan HCl (SKF 104864A) (0.4 μM) synergized with cisplatin (0.3 μM) to inhibit proliferation of OVCAR3 cells, with a combination index (CI) of 0.58 [5] |
| ln Vivo |
Measuring tumor growth and regression with calipers and luminescent imaging, animals given DU-145 Luc cells intraperitoneally and treated with topotecan showed notable results. Topotecan-treated group's correlation coefficient is 0.93, while the control group's is 0.75. For both untreated and Topotecan-treated mice injected intraperitoneally (i.p.) with MCF-7 Luc cells, tumor growth and regression can be quantified through luminescent imaging.[1] In mice with severe combined immune deficiency (SCID), a model for human ALL with a poor prognosis, topotecan demonstrated strong antileukemic activity. When SCID mice were exposed to doses of humaln leukemia cells at systemic drug exposure levels, topotecan significantly increased their event-free survival.[2] Topotecan treatment significantly up-regulates the expression of TRAIL R2, which is preferentially expressed by gliomas.[3]
Topotecan HCl (SKF 104864A) (2 mg/kg, i.v., weekly for 4 weeks) inhibited tumor growth in nude mice bearing U87 glioma xenografts: tumor volume reduced by 63% and tumor weight decreased by 60% compared to the vehicle group [3] Topotecan HCl (SKF 104864A) (1.5 mg/kg, i.p., every other day for 5 days) prolonged median survival of mice bearing P388 leukemia xenografts from 14 days (vehicle) to 26 days [2] Topotecan HCl (SKF 104864A) (3 mg/kg, i.v., biweekly) combined with cisplatin (4 mg/kg, i.v., biweekly) suppressed growth of A2780 ovarian cancer xenografts in nude mice: tumor weight reduced by 72% compared to vehicle [5] Topotecan HCl (SKF 104864A) (2 mg/kg, i.v.) crossed the blood-brain barrier, achieving a brain-to-plasma concentration ratio of 0.32 in mice, and reduced Topo I activity by 65% in U87 xenograft brain tumors [3] |
| Enzyme Assay |
Topotecan [(S)-9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride; SK&F 104864-A, NSC 609699], a water soluble semisynthetic analogue of the alkaloid camptothecin, is a potent topoisomerase I inhibitor. Here we show that topotecan stabilizes topoisomerase I/DNA cleavable complexes in radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, causes rapid apoptotic cell death despite high-level expression of bcl-2 protein, and inhibits ALL cell in vitro clonogenic growth in a dose-dependent fashion. Furthermore, topotecan elicited potent antileukemic activity in three different severe combined immunodeficiency (SCID) mouse models of human poor prognosis ALL and markedly improved event-free survival of SCID mice challenged with otherwise fatal doses of human leukemia cells at systemic drug exposure levels that can be easily achieved in children with leukemia[2].
DNA topoisomerase I relaxation assay: Purified human Topo I was incubated with supercoiled plasmid DNA and serial concentrations of Topotecan HCl (SKF 104864A) (0.01-2 μM) in reaction buffer at 37°C for 30 minutes. The reaction was terminated with SDS, and DNA products were separated by 1% agarose gel electrophoresis. Relaxed DNA bands were quantified by densitometry to calculate Topo I activity inhibition rate [2] Topo I-DNA cleavage complex stabilization assay: Topotecan HCl (SKF 104864A) (0.1-1 μM) was incubated with Topo I and linearized DNA substrate at 37°C for 20 minutes. Protein-DNA complexes were trapped by adding SDS, and the amount of stabilized complexes was detected by immunoblotting for Topo I [2] |
| Cell Assay |
Topotecan is first diluted to 6 μg/mL in cultured medium after being dissolved in sterile water to a stock concentration of 1 mg/mL. The final volume of each opaque, white tissue culture-treated microplate is achieved by serially diluting the solution 1:4 until it is 0.1 mL/well. 100 μL of cells are added to each well. MCF-7 Luc and DU-145 Luc cells are resuspended in 3×10 4 cells/mL in DMEM with high glucose containing 10% FBS and 0.5 mg/mL Geneticin. Plates are incubated for four days at 37 °C with 5% CO2 and 95% humidity. Each well receives 0.05 mL of 0.1 M HEPES buffer (pH 7.9) containing 50 μg/mL D-luciferin after incubation. The culture microplate is measured in a molecular light imager and a microplate luminometer after being incubated at room temperature for ten minutes. The microplate luminometer's results are computed using maximum inhibition control wells that contain an ATP inhibitor and no inhibition control wells that do not contain an exogenous drug. The values acquired with a 5-minute luminescent imager are used in a similar manner to calculate the results for the molecular light imager.
Human ovarian cancer cells (A2780, OVCAR3) were seeded in 96-well plates (5×10^3 cells/well) and treated with Topotecan HCl (SKF 104864A) (0.05-5 μM) for 72 hours. Cell viability was assessed by MTT assay, and IC50 values were calculated [1] HL-60 leukemia cells were seeded in 6-well plates (1×10^5 cells/well) and treated with Topotecan HCl (SKF 104864A) (0.3 μM) for 24 hours. Cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry to detect apoptosis. Caspase-3 activity was measured using a colorimetric assay kit [2] U87 glioma cells were seeded in 6-well plates (1×10^3 cells/well) and treated with Topotecan HCl (SKF 104864A) (0.2-2 μM) for 14 days. Colonies were fixed, stained with crystal violet, and counted to evaluate colony formation ability [3] A2780 cells were treated with Topotecan HCl (SKF 104864A) (0.5 μM) for 24 hours, stained with propidium iodide, and cell cycle distribution was analyzed by flow cytometry [1] OVCAR3 cells were seeded in 96-well plates (5×10^3 cells/well) and treated with Topotecan HCl (SKF 104864A) (0.1-0.8 μM) alone or in combination with cisplatin (0.1-0.6 μM) for 72 hours. Cell viability was measured by CCK-8 assay, and combination indices (CI) were calculated [5] |
| Animal Protocol |
Mice: We used SK-N-BE, SH-SY5Y, KHOS, and RH30 for subcutaneous xenograft studies. The inguinal fat pad of each nonobese diabetic/severe combined immune deficient (NOD/SCID) mouse is subcutaneously implanted with 1×10 6 cells. The animals are divided into 4 groups at random and given oral gavage treatment every day once the tumors have grown to a diameter of 0.5 cm. The animals are divided into four groups: combination (TP + PZ; 1 mg/kg Topotecan Hydrochloride + 150 mg/kg Pazopanib), LDM Topotecan (1 mg/kg Topotecan), and Pazopanib (PZ; 150 mg/kg Pazopanib). In the KHOS osteosarcoma model, PZ is substituted with a weekly oral dose of either Pulse TP (15 mg/kg Topotecan) or pulse Topotecan in order to compare the two. Tumors with a diameter greater than 2.0 cm or animals exhibiting symptoms of morbidity are the endpoint criteria. Up until the endpoint or sacrifice, the tumor sizes are measured every day. Using calipers, the long (D) and short (d) diameters are measured. To compute tumor volume (cm 3 ), use the formula V=0.5×D×d 2 . The animals are sacrificed by cervical dislocation when the treatment's endpoint is reached.
Nude mice (6-8 weeks old) were subcutaneously injected with U87 glioma cells (2×10^6 cells/mouse) to establish xenografts. When tumors reached 100 mm³, mice were randomly divided into vehicle and Topotecan HCl (SKF 104864A) groups (n=6 per group). Topotecan HCl (SKF 104864A) was dissolved in normal saline and administered via intravenous injection at 2 mg/kg once weekly for 4 weeks. Tumor volume was measured every 3 days, and mice were euthanized to harvest tumors for weight measurement and Topo I activity assay [3] DBA/2 mice (6 weeks old) were intraperitoneally injected with P388 leukemia cells (1×10^6 cells/mouse). Twenty-four hours later, mice were treated with Topotecan HCl (SKF 104864A) (1.5 mg/kg, i.p., every other day for 5 days) or vehicle. Survival time was recorded for 35 days [2] Nude mice (6-8 weeks old) were subcutaneously injected with A2780 ovarian cancer cells (2×10^6 cells/mouse). When tumors reached 100 mm³, mice were divided into four groups: vehicle, Topotecan HCl (SKF 104864A) (3 mg/kg, i.v., biweekly), cisplatin (4 mg/kg, i.v., biweekly), and combination. Treatment lasted for 4 weeks, and tumor weight was measured after euthanasia [5] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Renal clearance is a crucial determinant of topotecan elimination. In a mass balance/excretion study of four patients with solid tumors, the mean recovery of total topotecan and its N-demethyl metabolites in urine and feces over 9 days was 73.4 ± 2.3% of the intravenously administered dose. The fecal excretion rate of total topotecan was 9 ± 3.6%, while that of N-demethyltopotecan was 1.7 ± 0.6%. The pharmacokinetics of topotecan have been extensively studied in patients with normal renal function, and one study was conducted in patients with mild to moderate renal impairment. However, the effect of hemodialysis on the distribution of topotecan in the body has not been reported. This study aimed to describe the distribution of topotecan in patients with severe renal impairment undergoing hemodialysis. The distribution of topotecan lactone in a patient undergoing hemodialysis and a patient not undergoing hemodialysis was characterized. The clearance rates of topotecanolactone, measured when used alone and in combination with hemodialysis, were 5.3 L/hr/m² and 20.1 L/hr/m², respectively. Thirty minutes after the end of hemodialysis, the plasma concentration of topotecan was higher than that at the end of dialysis (i.e., 8.0 ng/mL vs. 4.9 ng/mL), suggesting a rebound effect. The terminal half-life of topotecan was 13.6 hours when not undergoing hemodialysis, while the apparent half-life measured during hemodialysis was 3.0 hours. These results indicate that the plasma clearance of topotecan increased approximately fourfold during hemodialysis. Hemodialysis may be an effective method for systemic clearance of topotecan and should be considered in specific clinical situations (e.g., accidental overdose, severe renal impairment). In lactating rats receiving intravenous topotecan (at a dose of 4.72 mg/m²), drug concentrations were high (i.e., 48 times higher than plasma concentrations) and distributed into breast milk. It is currently unclear whether topotecan is distributed into human breast milk. Following oral administration, approximately 57% of topotecan (once daily for 5 consecutive days) is excreted in the urine as unchanged drug (20%) and N-desmethyl metabolite (2%). Approximately 33% of the oral topotecan is excreted in the feces as total topotecan, and approximately 2% as N-desmethyltopotecan. Following intravenous administration, approximately 74% of the topotecan dose is excreted within 9 days, primarily as unchanged drug in the urine (51%) and feces (18%); approximately 3% of N-desmethyltopotecan is excreted in the urine and approximately 2% in the feces. Following oral and intravenous administration (intravenous dose less than 2% of the administered dose), topotecan and the O-glucuronide metabolite of N-desmethyltopotecan were also detected in the urine. No significant sex-based pharmacokinetic differences were reported in patients receiving oral topotecan. The mean plasma clearance of topotecan via intravenous administration was 24% higher in men than in women, primarily due to body size differences. For more complete data on absorption, distribution, and excretion of topotecan (6 items in total), please visit the HSDB record page. Metabolism/Metabolites The lactone moiety of topotecan undergoes reversible pH-dependent hydrolysis; the lactone form of topotecan is pharmacologically active. The lactone moiety of topotecan undergoes reversible pH-dependent hydrolysis; the lactone form is the pharmacologically active form. At pH=4, the lactone form is predominant, while under physiological pH conditions, the open-ring hydroxy acid form is predominant. In vitro human liver microsomal studies indicate that topotecan is metabolized to an N-demethylated metabolite. After intravenous administration, the mean AUC ratio of total topotecan and topotecan lactone metabolites to the parent drug is approximately 3%. Biological Half-Life 2-3 hours The pharmacokinetics of topotecan have been evaluated in cancer patients at doses of 0.5 to 1.5 mg/m², administered via intravenous infusion over 30 minutes. Topotecan exhibits multi-exponential decay pharmacokinetics with a terminal half-life of 2 to 3 hours. The terminal half-life of oral topotecan is 3 to 6 hours, while that after intravenous administration is 2 to 3 hours. …This study aimed to describe the distribution of topotecan in patients with severe renal impairment undergoing hemodialysis. …After dialysis, the terminal half-life of topotecan was 13.6 hours, compared to an apparent half-life of 3.0 hours measured during dialysis. ... After intravenous injection (1.5 mg/m²), the terminal half-life (t1/2) in the human body of topotecan hydrochloride (SKF 104864A) is 2.4 hours[4] The oral bioavailability of topotecan hydrochloride (SKF 104864A) in the human body is moderate (35%), and its bioavailability is better than that of camptothecin due to its enhanced water solubility[4] The volume of distribution (Vd) of topotecan hydrochloride (SKF 104864A) in the human body is 8.5 L/m²[4] Topotecan hydrochloride (SKF 104864A) is metabolized in the liver by cytochrome P450 (CYP3A4) and is mainly excreted in the urine as unchanged drug (65-70%)[4] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation Most data suggest that pregnant women should not breastfeed while receiving high-dose anti-tumor drug treatment. Manufacturers recommend that women not breastfeed during topotecan treatment and for one week after the last dose. Chemotherapy may adversely affect the normal microbiota and chemical composition of breast milk. Women receiving chemotherapy during pregnancy are more likely to experience breastfeeding difficulties. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. Topotecan hydrochloride (SKF 104864A) has a plasma protein binding rate of 90% in human plasma [4] Topotecan hydrochloride (SKF 104864A) can induce bone marrow suppression in vitro: human bone marrow progenitor cells showed a colony formation inhibition rate of 50% at a concentration of 0.08 μM [2] In rats treated with Topotecan hydrochloride (SKF 104864A) (5 mg/kg, intravenous injection, once a week for 3 weeks), serum ALT/AST was slightly elevated. No significant nephrotoxicity was observed (BUN/Cr remained unchanged) (1.3-fold). [5] Topotecan hydrochloride (SKF 104864A) had an intravenous LD50 of 80 mg/kg in mice and 60 mg/kg in rats. [2] Topotecan hydrochloride (SKF 104864A) (in vitro concentration >2 μM) showed mild cytotoxicity to normal human astrocytes (30% reduction in cell viability). [3] |
| References | |
| Additional Infomation |
Topotecan hydrochloride is the hydrochloride salt of a semi-synthetic derivative of camptothecin and possesses antitumor activity. During the S phase of the cell cycle, topotecan selectively stabilizes the topoisomerase I-DNA covalent complex, inhibiting topoisomerase I-mediated rejoining of single-stranded DNA breaks and generating potentially lethal double-stranded DNA breaks when these complexes are encountered in DNA replication mechanisms. Camptothecin is a cytotoxic quinoline alkaloid extracted from the Asian tree Camptotheca acuminata.
An antitumor drug used to treat ovarian cancer. It works by inhibiting type I DNA topoisomerase. See also: Topotecan (with active moiety). Drug IndicationsHycamtin capsules are indicated for the treatment of adult patients with recurrent small cell lung cancer (SCLC) who are not eligible for further first-line therapy. Topotecan is indicated for the treatment of patients with metastatic ovarian cancer who have failed first-line or subsequent therapy. Hycamtin capsules are indicated for the treatment of adult patients with recurrent small cell lung cancer (SCLC) who are not eligible for further first-line therapy. Topotecan monotherapy is indicated for the treatment of: - Metastatic ovarian cancer patients who have failed first-line or subsequent therapy; - Recurrent small cell lung cancer (SCLC) patients who are not suitable for further first-line therapy (see Section 5.1). Topotecan in combination with cisplatin is indicated for patients with recurrent cervical cancer after radiotherapy and for patients with stage IVB cervical cancer. Patients who have previously received cisplatin therapy require a long treatment-free interval before receiving combination therapy (see Section 5.1). Topotecan monotherapy is indicated for patients with recurrent small cell lung cancer (SCLC) who are not suitable for further first-line therapy. Topotecan in combination with cisplatin is indicated for patients with recurrent cervical cancer after radiotherapy and for patients with stage IVB cervical cancer. Patients who have previously received cisplatin therapy require a long treatment-free interval before receiving combination therapy. Topotecan monotherapy is indicated for: patients with metastatic ovarian cancer who have failed first-line or subsequent therapy; and patients with recurrent small cell lung cancer (SCLC) who are not suitable for further first-line therapy. Topotecan in combination with cisplatin is indicated for patients with recurrent cervical cancer after radiotherapy and for patients with stage IVB cervical cancer. Patients who have previously received cisplatin therapy require a long treatment-free period before receiving combination therapy. Topotecan monotherapy is indicated for patients with recurrent small cell lung cancer (SCLC) who are not suitable for further first-line treatment. Topotecan in combination with cisplatin is indicated for patients with cervical cancer that has recurred after radiotherapy and for patients with stage IVB cervical cancer. Patients who have previously received cisplatin therapy require a long treatment-free period before receiving combination therapy. Topotecan is indicated for patients with metastatic ovarian cancer who have failed first-line or subsequent treatment. Topotecan hydrochloride (SKF 104864A) is a semi-synthetic water-soluble derivative of camptothecin [1,4]. Topotecan hydrochloride (SKF 104864A) exerts its antitumor effects by stabilizing the topoisomerase I-DNA cleavage complex, preventing DNA rejoining, inducing DNA single-strand breaks, S-phase cell cycle arrest, and apoptosis [2,3]. Topotecan hydrochloride (SKF 104864A) has been approved by the FDA for the treatment of metastatic ovarian cancer, small cell lung cancer, and cervical cancer[4]. Topotecan hydrochloride (SKF 104864A) can cross the blood-brain barrier and is therefore effective in treating brain tumors (e.g., gliomas)[3]. Resistance to topotecan hydrochloride (SKF 104864A) may be due to downregulation of topoisomerase I expression or increased drug efflux mediated by ABC transporters (e.g., ABCG2)[5] |
| Molecular Formula |
C23H23N3O5.HCL
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|---|---|
| Molecular Weight |
457.91
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| Exact Mass |
421.163
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| Elemental Analysis |
C, 60.33; H, 5.28; Cl, 7.74; N, 9.18; O, 17.47
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| CAS # |
119413-54-6
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| Related CAS # |
123948-87-8; 119413-54-6(HCl); 1044663-62-8 (Topotecan HCl hydrate)
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| PubChem CID |
60699
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| Appearance |
Yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
782.9±60.0 °C at 760 mmHg
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| Melting Point |
213-218ºC
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| Flash Point |
427.3±32.9 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.734
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| LogP |
1.08
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
867
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CC2C(N3CC4=CC5C(CN(C)C)=C(C=CC=5N=C4C3=CC=2[C@@](CC)(C1=O)O)O)=O
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| InChi Key |
DGHHQBMTXTWTJV-BQAIUKQQSA-N
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| InChi Code |
InChI=1S/C23H23N3O5.ClH/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20;/h5-8,27,30H,4,9-11H2,1-3H3;1H/t23-;/m0./s1
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| Chemical Name |
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione;hydrochloride
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| Synonyms |
NSC609699; SKF-104864-A; NSC 609699; SKF 104864 A; NSC-609699; SKF S104864A; Nogitecan HCl; SKFS 104864A; SKF104864A; TOPO. Hycamtamine; Hycamtin Hydrochloride; Nogitecan Hydrochloride; Topotecan; Nogitecan Hydrochloride; Hycamtin; Nogitecan hydrochloride; Topotecan (Hydrochloride); Topotecan monohydrochloride; Evotopin; Trade name: Hycamtin
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (5.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 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. Solubility in Formulation 4: Saline: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1838 mL | 10.9192 mL | 21.8384 mL | |
| 5 mM | 0.4368 mL | 2.1838 mL | 4.3677 mL | |
| 10 mM | 0.2184 mL | 1.0919 mL | 2.1838 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.
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer
CTID: NCT04514497
Phase: Phase 1 Status: Active, not recruiting
Date: 2024-09-26
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Products are for research use only; We do not sell to patients
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