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 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 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 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 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.

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.

Antitumor Photosensitizer-4 (compound 10b), a conjugate of dasatinib and imatinib, serves as a potent tyrosine kinase inhibitor (TKI) targeting ABCG2. This photosensitizer (PS) induces apoptosis and reactive oxygen species (ROS) production, while demonstrating significant phototoxicity against both HepG2 and B16-F10 cells [1].

SJ 11646, a potent lymphocyte-specific protein tyrosine kinase (LCK) Degrader (PROTAC) with a DC50 of 0.00838 pM, utilizes Dasatinib as the LCK ligand and incorporates a phenyl glutarimide-based cereblon binder. Demonstrating cytotoxicity in both LCK-activated T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary leukemia samples in vitro, SJ 11646 also exhibits anti-leukemic efficacy in vivo within patient-derived xenograft models of T-ALL.