Dasatinib

Dasatinib (BMS-354825) is an orally active, ATP-competitive tyrosine kinase inhibitor that targets Src and Bcr-Abl (Ki=16/30 pM), with antitumor activity, used in the treatment of leukemia and lymphoma.

Dasatinib monohydrate (BMS-354825 Monohydrate) is an orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib monohydrate binds to and inhibits the growth-promoting activities of these kinases. Apparently, because of its less stringent binding affinity for the BCR-ABL kinase, Dasatinib monohydrate has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations.

Dasatinib hydrochloride (BMS-354825 HCl) (BMS-354825) hydrochloride is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib hydrochloride hydrochloride inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively. Dasatinib hydrochloride hydrochloride also induces Apoptosis and Autophagy.

Dasatinib N-oxide is a minor metabolite of Dasatinib.Dasatinib is an orally potent inhibitor of Src/Bcr-Abl.

Dasatinib D8 is deuterium-labeled dasatinib. Dasatinib is a dual Bcr-Abl and Src family tyrosine kinase inhibitor.

Dasatinib carbaldehyde (PROTAC ABL binding moiety 4) is based on Dasatinib which is an ABL inhibitor, binds to the IAP ligand via a linker, and forms SNIPER [1].

N-Deshydroxyethyl Dasatinib (N-Deshydroxyethyl BMS-354825) is a metabolite of Dasatinib, a dasatinib-based molecule that degrades ABL by binding to the IAP ligand via a linker to form SNIPER. N-Deshydroxyethyl Dasatinib is used in the study of cancer and immune diseases.

Dasatinib derivative 1 (2e) effectively releases nitric oxide (NO) and increases the concentration of 3’,5’-cyclic guanosine monophosphate (cGMP), while maintaining senescent cell-clearing activity. This compound can be utilized for research into chronic ocular hypertension (COHT) glaucoma.

Cisplatin/Dasatinib prodrug-1 (Compound 3) is a precursor drug for Cisplatin and Dasatinib. It exhibits antiproliferative activity against tumor cell lines A2780, MDA-MB-231, MCF7, HCT116, RD, Thp1, and HL60, with IC50 values of 0.1, 0.1, 0.36, 2.0, 0.4, 0.3, and 0.25 μM, respectively.

Pro-Dasatinib (compound 2j) is an amino acid analogue of Dasatinib and serves as a potent Src/Abl kinase inhibitor. It exhibits antiproliferative activity against K652 leukemia cancer cells, with an IC50 of 0.21 nM.

Gly-Dasatinib (compound I-7-1) is an amino acid analog of Dasatinib and functions as a tyrosine kinase inhibitor. It is utilized in cancer research.

N-Deshydroxyethyl Dasatinib-C3-NH2 is a target protein ligand-linker conjugate, comprising an LCK ligand and a PROTAC linker, designed to recruit E3 ligase. It is utilized in the synthesis of [PROTACSJ11646].

Dasatinib metabolite M6 (Dasatinib carboxylic acid) is an oxidative derivative of Dasatinib, a potent and orally active inhibitor of both Bcr-Abl and Src family tyrosine kinases[1].

Dasatinib analog-1 (compound 5826) demonstrates inhibition of CYP3A4 activity, presenting a K_i value of 5.4 μM, and effectively prevents the formation of glutathione adducts [1].

Hydroxymethyl dasatinib (M24), a benzylhydroxy metabolite of Dasatinib, demonstrates potent activity with an IC50 value of 46.7 nM in K562 CML cells [1].

SNIPER(ABL)-019, a compound that links Dasatinib (ABL inhibitor) to MV-1 (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels, exhibiting a DC50 of 0.3 μM[1].

SNIPER(ABL)-020 is a chemical compound consisting of Dasatinib, an ABL inhibitor, and Bestatin, an IAP ligand, conjugated with a linker. This compound effectively reduces the BCR-ABL protein[1].

SNIPER(ABL)-039, conjugating Dasatinib (ABL inhibitor) to an LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 10 nM. IC50s are 0.54 nM for ABL, 10 nM for cIAP1, 12 nM for cIAP2, and 50 nM for XIAP[1].

GL392 is a senolytic agent that delivers the potent senescence-clearing compound Dasatinib specifically to senescent cells. By targeting the LBD domain, it binds lipofuscin in these cells and releases Dasatinib via an ester linkage, inducing apoptosis (Apoptosis) in senescent cells. Additionally, GL392 is encapsulated in PEO-b-PCL microcapsules to ensure efficient intracellular delivery while minimizing systemic toxicity. GL392 is applicable in cancer research.

DA5-HTL is a compound that combines dasatinib with the HaloTag system, effectively inhibiting the growth of tumor cells, with a GI50 of 1.923 nM.

SJ11646 is a Dasatinib-based LCK PROTAC degrader with a DC50 of 0.00838 pM. It exhibits potent cytotoxicity against LCK-activated T-cell acute lymphoblastic leukemia (T-ALL) cells and primary leukemia samples, significantly prolongs LCK signal inhibition, and induces apoptosis in T-ALL cells. SJ11646 binds with high affinity to 51 human kinases, particularly ABL1, KIT, and DDR1. In mouse models of T-ALL, SJ11646 demonstrates exceptional anti-leukemic efficacy.

BMS-748730, also known as 4′-Hydroxy Dasatinib, is a Dasatinib metabolite.

SGX393 is an inhibitor of the CML mutant Bcr-AblT315I, thereby preempting in vitro resistance when combined with nilotinib or dasatinib.

APcK110 is a novel Kit inhibitor . APcK110 inhibits proliferation of the mastocytosis cell line HMC1.2 and the SCF-responsive cell line OCI/AML3 in a dose-dependent manner . APcK110 is a more potent inhibitor of OCI/AML3 proliferation than the clinically used Kit inhibitors imatinib and dasatinib and at least as potent as cytarabine. APcK110 inhibits the phosphorylation of Kit, Stat3, Stat5, and Akt in a dose-dependent fashion, showing activity of APcK110 on Kit and its downstream signaling pathways . APcK110 may have potent application in AML.