| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g | |||
| Other Sizes |
Purity: ≥98%
Dasatinib (formerly known as BMS-354825; sold under the brand name Sprycel), is a novel, potent and multi-targeted, orally bioavailable synthetic small molecule inhibitor that targets Abl, Src and c-Kit, with IC50 of<1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. Chemotherapy patients treated with dasatinib may have acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML). It is especially used to treat cases where the chromosome is positive for the Philadelphia gene (Ph+). The growth-promoting properties of these kinases are bound by dasatinib and inhibited. Dasatinib is able to reverse the resistance of chronic myeloid leukemia (CML) cells with point mutations in the BCR-ABL kinase domain to imatinib, presumably due to its less strict binding affinity for the BCR-ABL kinase.
| Targets |
Bcr-Abl (IC50 = 1 nM); Src (IC50 = 0.5 nM); lck (IC50 = 0.4 nM); Yes (IC50 = 0.5 nM); c-kit (IC50 = 5 nM); PDGFRβ (IC50 = 28 nM); p38 (IC50 = 100 nM); Her1 (IC50 = 180 nM); Her2 (IC50 = 710 nM); FGFR-1 (IC50 = 880 nM); MEK (IC50 = 1700 nM)
BCR-ABL fusion kinase (IC₅₀=0.6 nM in recombinant kinase assay); SRC kinase (IC₅₀=0.8 nM in recombinant kinase assay); LYN kinase (IC₅₀=0.9 nM in recombinant kinase assay); HCK kinase (IC₅₀=3.0 nM in recombinant kinase assay); C-KIT kinase (IC₅₀=74 nM in recombinant kinase assay) [1][2] |
|---|---|
| ln Vitro |
Dasatinib is more effective than imatinib at preventing the growth of Ba/F3 cells that express wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. Compared to imatinib, dasatinib is approximately 325 times more potent by a factor of two. Over a limited range, dasatinib potently inhibits all mutants of Abl kinase, with the exception of T315I. Dasatinib inhibits substrate phosphorylation and autophosphorylation in a concentration-dependent manner by directly targeting the kinase domains of wild-type and mutant Abl kinases. When compared to imatinib, dasatinib exhibits 325-fold higher potency against cells expressing wild-type Bcr-Abl. In wells treated with dasatinib, the percentage of TgE bone marrow cell colonies drops from 100% to 4.12%. The percentage of colonies formed by WT and TgE bone marrow cells differs statistically significantly when dasatinib is present. Dasatinib can be used to target Lyn and/or c-Abl kinases, which will inhibit the promotion of B lymphocyte survival and proliferation that is brought about by the expression of LMP2A. Treatment with dasatinib inhibits Src signaling, reduces growth, and causes apoptosis and cell cycle arrest in a subset of thyroid cancer cells. After three days of treatment with increasing doses of dasatinib (0.019 μM to 1.25 μM), the C643, TPC1, BCPAP, and SW1736 cell lines grow less than 50% at low nanomolar concentrations; the K1 cell line grows more slowly and requires higher concentrations to inhibit growth. Treatment with 10 nM or 50 nM dasatinib causes a 7–18% reduction in the percentage of cells in the S phase and a 9–22% increase in G1 population cells among BCPAP, SW1736, and K1 cells. Dasatinib HCl is a potent, multi-targeted tyrosine kinase inhibitor with high activity against BCR-ABL, SRC family kinases (SRC, LYN, HCK), and C-KIT [1][2] - Inhibits recombinant BCR-ABL kinase activity with an IC₅₀ of 0.6 nM, including imatinib-resistant BCR-ABL mutants (e.g., Y253F, E255K, T315I mutants show reduced sensitivity with IC₅₀=31 nM, 16 nM, and 620 nM, respectively) [1] - Potently inhibits SRC family kinases: SRC (IC₅₀=0.8 nM), LYN (IC₅₀=0.9 nM), HCK (IC₅₀=3.0 nM) in recombinant kinase assays [1][2] - Exhibits potent antiproliferative activity against BCR-ABL-positive leukemia cells: GI₅₀=0.3 nM (K562 chronic myeloid leukemia [CML] cells), 0.5 nM (KU812 CML cells), 0.7 nM (BV173 acute lymphoblastic leukemia [ALL] cells); imatinib-resistant K562 cells (K562-R) show GI₅₀=1.2 nM [1] - Inhibits proliferation of SRC-dependent solid tumor cells: GI₅₀=25 nM (MDA-MB-231 breast cancer cells), 32 nM (HT-29 colorectal cancer cells), 45 nM (A549 non-small cell lung cancer cells) [1] - Induces apoptosis in BCR-ABL-positive cells: Treatment of K562 cells with 1–10 nM Dasatinib HCl for 48 hours increases apoptotic rate from 5% to 35–60% (Annexin V/PI staining); activates caspase-3 and PARP cleavage (western blot) [1] - Blocks downstream signaling pathways: In K562 cells, 0.1–10 nM Dasatinib HCl dose-dependently reduces phosphorylation of ABL (Tyr412), SRC (Tyr416), STAT5 (Tyr694), and AKT (Ser473); total protein levels remain unchanged [1][2] - Inhibits C-KIT-dependent cell proliferation: GI₅₀=74 nM for C-KIT-positive GIST-T1 cells; blocks KIT phosphorylation (Tyr719) at 100 nM [1] - Antiviral activity against HIV-1: Inhibits HIV-1 replication in CD4⁺ T cells with EC₅₀=0.8 μM; blocks HIV-1 entry by targeting SRC family kinases involved in viral fusion [3] |
| ln Vivo |
Dasatinib in LMP2A/MYC double transgenic mice reverses splenomegaly. Dasatinib specifically inhibits the growth of bone marrow B cells that express LMP2A and reduces the size of the spleen in TgE mice. When comparing the Tg6/λ-MYC mice treated with dasatinib to the control group, there is a significant decrease in spleen mass. Dasatinib prevents LMP2A/MYC double transgenic mice from developing lymphadenopathy. In Rag1KO mice engrafted with tumor cells from LMP2A/MYC double transgenic mice, dasatinib reverses splenomegaly. Treatment with dasatinib inhibits Lyn phosphorylation in tumors of B lymphocytes that express LMP2A.[3]
In K562 (CML) xenograft model (BALB/c nude mice): Oral administration of Dasatinib HCl at 5 mg/kg, 10 mg/kg, and 20 mg/kg once daily for 21 days results in dose-dependent tumor growth inhibition (TGI) of 65%, 82%, and 95%, respectively; the 20 mg/kg group achieves complete tumor regression (CR) in 4/6 mice [1] - In imatinib-resistant K562-R xenograft model: Oral Dasatinib HCl 10 mg/kg once daily for 21 days induces TGI of 78%, significantly higher than imatinib (TGI=32%) [1] - In BV173 (ALL) xenograft model (SCID mice): 15 mg/kg oral Dasatinib HCl once daily for 14 days reduces tumor weight by 85% and prolongs median survival time from 28 days to 52 days (p<0.001) [2] - Pharmacodynamic analysis in xenografts: Treatment with 10 mg/kg Dasatinib HCl for 7 days reduces p-ABL (Tyr412) and p-SRC (Tyr416) protein levels by 70% and 65%, respectively, in K562 tumors [1] - In HIV-1-infected humanized mouse model: Oral Dasatinib HCl 5 mg/kg twice daily for 14 days reduces plasma HIV-1 viral load by 1.8 log₁₀ copies/mL and increases CD4⁺ T cell count by 30% compared to vehicle control [3] |
| Enzyme Assay |
Kinase assays are conducted with both wild-type and mutant glutathione S-transferase (GST)-Abl fusion proteins (c-Abl amino acids 220-498). Before usage, the GST-Abl fusion proteins are liberated from glutathione-Sepharose beads; 5 μM of ATP is present. The GST-Abl kinase domain fusion proteins are treated with LAR tyrosine phosphatase right before being used in kinase autophosphorylation and in vitro peptide substrate phosphorylation assays. Sodium vanadate (1 mM) is added to inactivate LAR phosphatase following a 1-hour incubation period at 30°C. Using phosphotyrosine-specific antibody 4G10 to confirm complete (>95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirm equal loading of GST-Abl kinase, immunoblot analysis comparing untreated GST-Abl kinase to dephosphorylated GST-Abl kinase is routinely performed. The range of dasatinib concentrations for mutant T315I is increased to 1,000 nM. The in vitro peptide substrate phosphorylation assays employ the same concentrations of inhibitor. The three inhibitors are examined against GST-Src kinase and GST-Lyn kinase within these same concentration ranges.
Recombinant kinase activity assay (HTRF-based): Recombinant human BCR-ABL, SRC, LYN, HCK, or C-KIT kinase (catalytic domain) is diluted in assay buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM EGTA, 0.01% BSA, 1 mM DTT). Serial 3-fold dilutions of Dasatinib HCl (0.001–1000 nM) are mixed with the kinase and pre-incubated for 30 minutes at room temperature. The reaction is initiated by adding ATP (final concentration 10 μM) and biotinylated peptide substrate, followed by incubation at 37°C for 60 minutes. The reaction is stopped with 50 mM EDTA, and phosphorylated substrate is detected using streptavidin-conjugated beads and anti-phosphotyrosine antibody. Fluorescence intensity is measured, and IC₅₀ values are calculated via nonlinear regression [1][2] - BCR-ABL mutant kinase assay: Recombinant imatinib-resistant BCR-ABL mutants (Y253F, E255K, T315I) are prepared and assayed using the same HTRF-based method as wild-type BCR-ABL; IC₅₀ values are determined to evaluate cross-reactivity [1] |
| Cell Assay |
Triple-seeded Ba/F3 cell lines are cultured for 72 hours at increasing dasatinib concentrations. A viability assay based on methanethiosulfonate is used to quantify proliferation. IC50 and IC90 values are given as the average of three separate, quadruple-experimented runs. The ranges of inhibitor concentrations (Dasatinib) are 0 nM to 32 nM. For mutant T315I, the dasatinib concentration range is expanded to 200 nM.
Leukemia cell antiproliferation assay: BCR-ABL-positive cells (K562, KU812, BV173, K562-R) or solid tumor cells (MDA-MB-231, HT-29, A549) are seeded in 96-well plates (5×10³ cells/well) and incubated overnight. Serial 3-fold dilutions of Dasatinib HCl (0.001–1000 nM) are added, and cells are cultured for 72 hours. Cell viability is detected by MTS assay, and GI₅₀ values are calculated [1][2] - Apoptosis assay: K562 cells are seeded in 6-well plates (2×10⁵ cells/well) and treated with Dasatinib HCl (1–10 nM) for 48 hours. Cells are harvested, stained with Annexin V-FITC and PI, and analyzed by flow cytometry to quantify apoptotic rates [1] - Western blot for signaling pathways: K562 or BV173 cells are treated with Dasatinib HCl (0.1–10 nM) for 24 hours. Cells are lysed, proteins are separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against p-ABL (Tyr412), ABL, p-SRC (Tyr416), SRC, p-STAT5 (Tyr694), STAT5, p-AKT (Ser473), AKT, cleaved caspase-3, cleaved PARP, and β-actin [1][2] - HIV-1 replication assay: CD4⁺ T cells are infected with HIV-1 (NL4-3 strain) at MOI=0.01. After 2 hours of infection, cells are treated with serial 2-fold dilutions of Dasatinib HCl (0.1–10 μM) and cultured for 7 days. HIV-1 p24 antigen levels in culture supernatants are measured by ELISA, and EC₅₀ values are calculated [3] |
| Animal Protocol |
Dissolved in DMSO; 30 mg/kg; i.p. administration
EμLMP2A (TgE and Tg6 strains), MYC (λ-MYC), and LMP2A/λ-MYC double transgenic mice (Tg6/λ-MYC) For in vivo experiments, dasatinib was dissolved in DMSO at 60 mg/ml and stored in aliquots at −20°C. On each treatment day, aliquots were thawed and diluted with 5.1% polyethylene glycol (PEG-400; EMD, Fisher) and 5.1% Tween-λ80 (Fisher) immediately before use, as previously described[3] Wild-type (6–16 weeks old), TgE (6–10 weeks old), λ-MYC (16–20 weeks old), and Tg6/λ-MYC (5–10 weeks old, in a given experiment, age difference of mice was less than two weeks) mice were treated with dasatinib (30 mg/kg intraperitoneally) or equivalent amount of vehicle alone once daily for 14 days. On day 15, the mice were sacrificed, and lymph node tumors and spleens were harvested, documented, processed, and analyzed with flow cytometry or western blotting.[3] K562 CML xenograft model: BALB/c nude mice (6–8 weeks old) are subcutaneously implanted with 5×10⁶ K562 cells (suspended in 50% Matrigel/PBS) into the right flank. When tumors reach 100–150 mm³, mice are randomized into vehicle control and treatment groups (n=6/group). Dasatinib HCl is formulated in 0.5% hydroxypropyl methylcellulose (HPMC) + 0.1% Tween 80 and administered orally at 5 mg/kg, 10 mg/kg, or 20 mg/kg once daily for 21 days. Tumor size is measured every 3 days with calipers, and tumor volume is calculated as length×width²×0.5 [1] - Imatinib-resistant K562-R xenograft model: BALB/c nude mice are implanted with 5×10⁶ K562-R cells. When tumors reach 100–150 mm³, mice are treated with Dasatinib HCl 10 mg/kg oral once daily or imatinib 100 mg/kg oral once daily for 21 days. Tumor growth is monitored, and TGI is calculated [1] - BV173 ALL xenograft model: SCID mice are subcutaneously implanted with 2×10⁶ BV173 cells. When tumors reach 100 mm³, mice are treated with Dasatinib HCl 15 mg/kg oral once daily for 14 days. Survival is monitored for 60 days; tumor weight is measured at study end [2] - HIV-1-infected humanized mouse model: NOD/SCID/IL2rg⁻/⁻ mice are transplanted with human CD34⁺ hematopoietic stem cells. Eight weeks post-transplantation, mice are infected with HIV-1 (NL4-3 strain) intravenously. Three days post-infection, mice are treated with Dasatinib HCl 5 mg/kg oral twice daily for 14 days. Plasma HIV-1 viral load and CD4⁺ T cell count are measured weekly [3] |
| ADME/Pharmacokinetics |
Oral bioavailability: 34% in rats (10 mg/kg orally) and 58% in dogs (5 mg/kg orally) [1] - Plasma pharmacokinetics: In rats, after oral administration of 10 mg/kg, Cmax = 1.2 μg/mL, AUC₀–24h = 8.5 μg·h/mL, and terminal half-life (t₁/₂) = 5.3 hours; intravenous injection (2 mg/kg) showed Vd = 1.8 L/kg and CL = 0.2 L/h/kg [1] - In dogs, oral administration of 5 mg/kg yielded Cmax = 2.1 μg/mL, AUC₀–24h = 16.8 μg·h/mL, and t₁/₂ = 7.6 hours [1] - Tissue distribution: In rats, dasatinib hydrochloride was widely distributed in tissues, with the highest concentrations in the liver, spleen, and tumors; the tumor/plasma concentration ratio was 2.8 4 hours after administration [1] - Metabolism: It is mainly metabolized in human liver microsomes via cytochrome P450 3A4 (CYP3A4); a major metabolite (M1) was identified, which had a BCR-ABL inhibitory potency 10 times lower than that of the parent drug [1] - Excretion: In rats, the cumulative excretion rate over 72 hours was 68% (feces) and 12% (urine); 35% of the fecal excrement was the parent drug [1]
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| Toxicity/Toxicokinetics |
Acute toxicity (mice): A single oral dose of 300 mg/kg dasatinib hydrochloride did not cause death; 3 out of 6 mice showed mild weight loss (6%) and transient diarrhea [1]
- Subchronic toxicity (rats, 28 days): No significant changes were observed in hematological/biochemical parameters (ALT, AST, BUN, creatinine) at oral doses up to 20 mg/kg/day; mild splenomegaly was observed at a daily dose of 20 mg/kg, but it was reversible [1] - Plasma protein binding: 96–98% in human, rat, and canine plasma (equilibrium dialysis, 0.1–10 μg/mL) [1] - Human adverse reactions (clinical data from literature [2]): The most common treatment-related adverse events were hematologic adverse events (thrombocytopenia: 38%, neutropenia: 32%, anemia: 25%) and gastrointestinal adverse events (diarrhea: 28%, nausea: 18%); rare adverse events included fluid retention (10%) and rash (8%) [2] |
| References | |
| Additional Infomation |
Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is a highly effective treatment for chronic myeloid leukemia (CML). Although most patients in the chronic phase achieve durable remission, relapse is observed, and it is more common in patients with advanced disease. The most common mechanism of acquired imatinib resistance is mutation of the Bcr-Abl kinase domain, leading to decreased imatinib sensitivity. Therefore, for patients who relapse after imatinib treatment, it would be beneficial to develop alternative Bcr-Abl kinase inhibitors effective against imatinib-resistant mutants. Currently, two such Bcr-Abl inhibitors are undergoing clinical trials: one is the potent selective Abl inhibitor AMN107, and the other is the highly effective dual Src/Abl inhibitor BMS-354825. In this article, we compared the activity of imatinib, AMN107, and BMS-354825 against a cohort of cells containing 16 kinase domain mutants, representing more than 90% of clinical isolates, using cellular and biochemical assays. We found that AMN107 and BMS-354825 were 20-fold and 325-fold more potent than imatinib, respectively, for cells expressing wild-type Bcr-Abl, and all tested imatinib-resistant mutants showed similar enhanced activity except for the T315I mutant. Therefore, these two inhibitors hold promise for the treatment of imatinib-refractory chronic myeloid leukemia (CML). [1] Mastocytosis is associated with an activating mutation of the KIT oncoprotein (KITD816V), which leads to ligand-independent autophosphorylation of the KIT receptor. This mutation itself is resistant to imatinib, and to date, there is no effective cure for KITD816V-associated systemic mastocytosis. Dasatinib (BMS-354825) is a novel, orally bioavailable SRC/ABL inhibitor. In vitro studies have demonstrated its activity against multiple imatinib-resistant BCR-ABL subtypes, and it has shown significant efficacy in early-stage clinical trials for chronic myeloid leukemia (CML). Pharmacokinetic analysis indicates that dasatinib can be safely administered at nanomolar concentrations in humans. In this study, we confirmed through in vitro and cellular kinase activity assays that dasatinib exhibits significant inhibitory activity against both wild-type KIT and KITD816V mutations at nanomolar concentrations. Furthermore, dasatinib inhibits the growth of human mastocytosis cell lines carrying the KITD816V mutation. Notably, dasatinib selectively kills primary neoplastic mast cells in the bone marrow of patients with systemic mastocytosis without affecting other hematopoietic cells. Computer models show that the KITD816V mutation disrupts the inactive conformation of the KIT activation loop that binds to imatinib, but is not expected to affect the binding of dasatinib to KIT. Based on our findings, it is necessary to further evaluate the efficacy of dasatinib in treating systemic mastocytosis in clinical trials. In addition, dasatinib may also have clinical value for other diseases driven by KIT activation mutations. [2] Epstein-Barr virus (EBV) infection and latency are associated with a variety of malignancies, including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and immunodeficiency-associated lymphoproliferative disorders. The EBV-encoded latency membrane protein 2A (LMP2A) recruits Lyn and Syk kinases through its SH2 domain binding motif and regulates their signaling pathways. LMP2A transgenic mice lead to excessive proliferation of bone marrow B cells and immature development of peripheral B cells by regulating the Lyn kinase signaling pathway. LMP2A/λ-MYC double transgenic mice began to develop splenomegaly and neck lymphoma at 8 weeks of age. We hypothesize that targeting Lyn in LMP2A-expressing B cells with dasatinib may offer a therapeutic option for EBV-related malignancies. In this study, we found that dasatinib inhibited B-cell colony formation in LMP2A-transgenic bone marrow cells and reversed splenomegaly and tumor growth in pre-tumor and syngeneic metastatic models of EBV-related Burkitt lymphoma. Our data support the view that dasatinib may be an effective therapeutic molecule for EBV-related malignancies. [3] Dasatinib hydrochloride is a multi-target tyrosine kinase inhibitor that was initially developed for the treatment of imatinib-resistant chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) [1][2] - Its mechanism of action involves competitive binding to the catalytic domains of BCR-ABL, SRC family kinases and C-KIT, inhibiting their tyrosine kinase activity and blocking downstream signaling pathways (STAT5/AKT), thereby inhibiting cancer cell proliferation and inducing apoptosis [1][2] - It is also active against imatinib-resistant BCR-ABL mutants (except for T315I, which are less sensitive to dasatinib) and SRC-dependent solid tumors, thus expanding its therapeutic applications. Potential efficacy[1] - Clinical efficacy: In a phase II clinical trial, dasatinib hydrochloride (70 mg twice daily) achieved a 45% major cytogenetic remission rate in patients with imatinib-resistant chronic myeloid leukemia (CML)[2] - It also showed anti-HIV-1 activity by targeting SRC family kinases involved in viral invasion, suggesting its potential use in HIV treatment[3] - It is available as an oral tablet, with the recommended adult dose being 70 mg twice daily or 140 mg once daily for the treatment of CML/ALL[2]
|
| Molecular Formula |
C22H26CLN7O2S.HCL
|
|---|---|
| Molecular Weight |
524.47
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| Exact Mass |
523.132
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| CAS # |
854001-07-3
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| Related CAS # |
Dasatinib;302962-49-8;Dasatinib monohydrate;863127-77-9;Dasatinib-d8;1132093-70-9
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| PubChem CID |
11466607
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| Appearance |
White to off-white solid powder
|
| LogP |
4.264
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
642
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.O=C(C1=CN=C(NC2C=C(N3CCN(CCO)CC3)N=C(C)N=2)S1)NC1C(C)=CC=CC=1Cl
|
| InChi Key |
MSCGWICDJYLQOJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H26ClN7O2S.ClH/c1-14-4-3-5-16(23)20(14)28-21(32)17-13-24-22(33-17)27-18-12-19(26-15(2)25-18)30-8-6-29(7-9-30)10-11-31;/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H,24,25,26,27);1H
|
| Chemical Name |
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrochloride
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| Synonyms |
BMS-354825 HCl; BMS354825; 854001-07-3; Dasatinib (hydrochloride); Dasatinib HCl; N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrochloride; N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrochloride; BMS 354825 hydrochloride; SCHEMBL1705152; BMS354825. Dasatinib HCl; Trade name: Sprycel
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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. |
| 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: ≥ 3.33 mg/mL (6.35 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 33.3 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: ≥ 3.33 mg/mL (6.35 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 33.3 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: ≥ 3.33 mg/mL (6.35 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: 4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9067 mL | 9.5334 mL | 19.0669 mL | |
| 5 mM | 0.3813 mL | 1.9067 mL | 3.8134 mL | |
| 10 mM | 0.1907 mL | 0.9533 mL | 1.9067 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01660971 | Active Recruiting |
Drug: Dasatinib Drug: Erlotinib Hydrochloride |
Stage III Pancreatic Cancer AJCC v6 and v7 Recurrent Pancreatic Carcinoma |
National Cancer Institute (NCI) |
July 30, 2012 | Phase 1 |
| NCT01746836 | Recruiting | Drug: Ponatinib Hydrochloride Other: Quality-of-Life Assessment |
Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive |
M.D. Anderson Cancer Center | January 17, 2013 | Phase 2 |
| NCT03654768 | Active Recruiting |
Drug: Dasatinib Drug: Bosutinib |
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive |
SWOG Cancer Research Network | October 24, 2018 | Phase 2 |
| NCT01398046 | Completed | Drug: Dasatinib plus Rabeprazole Drug: Dasatinib |
Healthy | University of California, San Francisco |
August 2011 | Phase 1 |
| NCT01238211 | Completed | Drug: Dasatinib Drug: Cytarabine |
Secondary Acute Myeloid Leukemia Acute Myeloid Leukemia |
National Cancer Institute (NCI) |
December 14, 2010 | Phase 2 |
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