Dasatinib

Product Overview

Dasatinib (development code BMS-354825), developed by Bristol-Myers Squibb and marketed as Sprycel, ATC code L01XE06, is a second-generation oral tyrosine kinase inhibitor (TKI).

Structural class: an aminopyrimidine compound — a 2-methylpyrimidine core, with the 4-position linked via an amino group to 1,3-thiazole-5-carboxamide (the amide nitrogen bearing a 2-chloro-6-methylphenyl group), and the 6-position bearing a 4-(2-hydroxyethyl)piperazin-1-yl group. The thiazole carboxamide and the 2-chloro-6-methylaniline moieties are the key pharmacophores for binding to the kinase hinge region and hydrophobic pocket.

Dual inhibition and potency: simultaneously inhibits the BCR-ABL fusion protein and Src family kinases. IC50 values against Abl, Src, c-Kit (wild-type), and c-Kit D816V are approximately 0.6, 0.8, 79, and 37 nM, respectively — several hundred times more potent than imatinib against Abl and Src.

Structural basis for overcoming imatinib resistance: dasatinib adapts better to ABL kinase conformations — it can bind both the active (DFG-in) and inactive (DFG-out) conformations of the kinase, and therefore retains activity against most BCR-ABL point mutations that confer imatinib resistance (except the T315I mutation). In addition, its inhibition of Src family kinases enables it to act on pathways not covered by imatinib.

Pharmacokinetic profile: orally absorbed; absolute bioavailability approx. 15% (literature data); plasma protein binding approx. 96%; apparent volume of distribution approx. 6.3 L/kg; extensively metabolized mainly via CYP3A4; transporters involved include ABCB1 (P-gp) and ABCG2 (BCRP). Water solubility is extremely low (approx. 1.28×10⁻² g/L), making it a BCS class II molecule, and absorption depends on gastric pH — proton pump inhibitors and H₂ receptor antagonists significantly reduce its exposure, a clinically important interaction point.

Technical Specifications

• Standards: CHP／USP／EP

• Specification: 0.99 (purity ≥99.0%, HPLC); reagent grade commonly ≥98% (HPLC)

• CAS No.: 302962-49-8 (anhydrate／free base, EINECS 801-607-0, MDL MFCD11046566, KEGG D03658, DrugBank DB01254, PubChem CID 3062316); the monohydrate has molecular formula C₂₂H₂₆ClN₇O₂S·H₂O, molecular weight 506.02; the hydrochloride salt is CAS 854001-07-3 (C₂₂H₂₇Cl₂N₇O₂S, MW 524.47) — these are three different substances and must not be used interchangeably

• Molecular formula: C₂₂H₂₆ClN₇O₂S

• Molecular weight: 488.01 (consistent across ChemicalBook, Xiamen University database, and 化工仪器网); calculated values of 488.006／488.007／488.013 also reported. Exact mass 487.1557

• Appearance: white to off-white solid powder; some sources describe it as a grayish-white to yellow solid (ChemicalBook records “White powder, White or off-white”; 科普中国 records “gray-white to yellow solid”)

• Purity (HPLC): ≥ 99.0%

• Melting point: 275–286 ℃ (consistent across ChemicalBook, Baidu Baike, 科普中国, MOLBASE, Guidechem, and other sources; recommended value); other sources record 280–286 ℃ (Xiamen University ADMETNet, ChemicalBook international page) — a narrowed statement of the same range. CAS 302962-49-8 corresponds to the anhydrate; the hydrochloride salt (854001-07-3) has a melting point of 279–280 ℃ and is a different substance. The above values come from literature/supplier standards, not from a publicly verifiable official pharmacopoeial melting point

• Specific optical rotation: not applicable — the molecule contains no chiral center (the piperazine ring can invert; no stereocenter)

• 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

• Stereochemistry: no stereocenters

• Solubility: freely soluble in DMSO (up to approx. 200 mg/mL; another source records 250 mg/mL, requiring sonication); practically insoluble in water (aqueous solubility approx. 1.28×10⁻² g/L, i.e., approx. 12.8 mg/L)

• Acid dissociation constant (pKa): 10.94 ± 0.70 (calculated)

• Calculated physicochemical parameters: density approx. 1.408 ± 0.06 g/cm³ (also recorded as 1.4 ± 0.1); LogP approx. 3.46 (calculated XLogP3 also recorded as 3.6; individual sources record 1.8／2.24 — the differences arise from calculation methods and must be noted when quoting); hydrogen bond donors 3／acceptors 9; rotatable bonds 7; topological polar surface area approx. 134.75–135 Ų; heavy atom count 33; refractive index approx. 1.688

• Marketed dosage forms: film-coated tablets in 20 mg, 50 mg, 70 mg, 100 mg, 140 mg, and other strengths (as dasatinib)

• Storage conditions: store sealed, dry, and frozen at −20 ℃, protected from light; DMSO solutions can be stored at −20 ℃ for up to 2 months

Applications

• Chronic myeloid leukemia (CML): for adult patients with chronic-phase, accelerated-phase, or myeloid or lymphoid blast-phase CML resistant or intolerant to prior therapy (including imatinib mesylate). The recommended dose for chronic phase is 100 mg orally once daily, which may be increased to 140 mg once daily based on efficacy and tolerability

• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL): for adult patients with Ph+ ALL resistant or intolerant to prior therapy

• Mechanism research: used for inhibition studies of targets including BCR-ABL and Src family kinases (SRC, LCK, YES, FYN), c-Kit, PDGFR, and Ephrin receptors; studies of ATP-competitive binding, kinase conformational selectivity (DFG-in／DFG-out), and resistance mutation profiles (including the T315I exception); and P-gp／BCRP transporter interaction studies

• Investigational/expansion directions: the literature reports exploratory research in solid tumors, acute myeloid leukemia, and combinations with immunotherapy — all of the above are investigational directions, not approved indications

• Formulation and manufacturing: used in formulation development of film-coated tablets; the API is practically insoluble in water and is a BCS class II compound, so formulations must focus on solubilization and dissolution, and take into account its gastric pH-dependent absorption characteristics; key manufacturing control points include related substances (particularly piperazine side-chain-related impurities and residual chloroaniline), assay, polymorphic form, and residual solvents; suitable for analytical method development and validation, stability studies, impurity reference standards, and GMP scale-up and CMO／CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended only for legitimate industrial, research, and pharmaceutical manufacturing use; it is not for end-user clinical use or self-medication guidance. The finished product is a prescription drug that must be prescribed by a physician experienced in antineoplastic therapy, with regular monitoring. Key warnings: ① Myelosuppression — may cause neutropenia, thrombocytopenia, and anemia; frequent complete blood count monitoring is required early in treatment; ② Fluid retention — including pleural effusion, pericardial effusion, pulmonary edema, and peripheral edema, which may cause dyspnea; monitor body weight and respiratory symptoms; ③ Pulmonary arterial hypertension (PAH) — has been reported and may be reversible upon discontinuation; ④ QT interval prolongation — correct hypokalemia or hypomagnesemia before and during treatment; ⑤ Bleeding events — including gastrointestinal and central nervous system hemorrhage, which can be fatal and are often associated with thrombocytopenia; ⑥ Cardiac toxicity／cardiac dysfunction; ⑦ Hepatotoxicity and hepatitis B reactivation. Additional risks include tumor lysis syndrome and growth retardation in pediatric patients. Drug interactions: avoid concomitant use with proton pump inhibitors, H₂ receptor antagonists, or antacids (elevated gastric pH significantly reduces dasatinib exposure); avoid concomitant use with strong CYP3A4 inhibitors or inducers (this product is metabolized mainly via CYP3A4). The API’s GHS classification includes skin irritation category 2, serious eye damage category 1, carcinogenicity category 2, reproductive toxicity category 2, specific target organ toxicity (repeated exposure) category 1, and chronic aquatic hazard category 1 (H315／H318／H351／H361／H372／H410). When handling, wear protective gloves, protective clothing, and respiratory and eye/face protection; avoid dust inhalation and avoid release to the environment.

Product information: please contact us. This information is for reference only.