Bcr-Abl Degrader

Asciminib-NH2 is a BCR-ABL ligand and can be used for the synthesis of PROTACs, such as P19As (HY-180981).

SIAIS100 TFA is a potent BCR-ABL PROTAC degrader with an DC₅₀ value of 2.7 nM. SIAIS100 TFA can be used to research chronic myeloid leukemia (CML).

N-Deshydroxyethyl Dasatinib (N-Deshydroxyethyl BMS-354825) is a metabolite of Dasatinib, Dasatinib is a multi-kinase inhibitor that potently inhibits Bcr-Abl, Src family and platelet-derived growth factor receptor kinases. N-Deshydroxyethyl Dasatinib can be used in cancer and immune disease research.

PROTAC BCR-ABL Degrader-1 is a PROTAC degrader targeting BCR-ABL, and also selectively inhibits cancer cell proliferation. PROTAC BCR-ABL Degrader-1 induces degradation via the ubiquitin-proteasome system to reduce protein levels. PROTAC BCR-ABL Degrader-1 can be used for research on chronic myeloid leukemia.

SB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research.

Leu-PEG1-Dasa is a potent BCR-ABL PROTAC degrader with a DC₅₀ of 0.48 nM. Leu-PEG1-Dasa uses a single amino acid as the E3 ligand and belongs to a mini-PROTAC, functioning through the N-terminal canonical pathway. Leu-PEG1-Dasa exhibits potent anti-proliferative activity against K562 cells. Leu-PEG1-Dasa can be used for the study of chronic myeloid leukemia (CML).

DS-PPE-GW is a BCR-ABL ATTEC degrader. DS-PPE-GW connects BCR-ABL and LC3B, thereby tethering BCR-ABL to the autophagosome membrane. DS-PPE-GW shows potent BCR-ABL degradation. DS-PPE-GW has anticancer activity against chronic myeloid leukemia (Pink: LC3B ligand (HY-10542); Blue: BCR-ABL ligand (HY-107447); Black: Linker (HY-W001860)).

BCR-ABL degrader 1 (Compound 23) is a HyT-based BCR-ABL degrader with a DC₅₀ of 19.9 μM. BCR-ABL degrader 1 can be used in the research of chronic myeloid leukemia.

Azo-PROTAC-4C-cis is a BCR-ABL PROTAC degrader, and its degradation efficiency of BCR-ABL is much lower than that of its trans isomer Azo-PROTAC-4C-trans (HY-180983). Azo-PROTAC-4C-cis is the product of the conformational transformation of Azo-PROTAC-4C-trans under ultraviolet (UV) light irradiation. Azo-PROTAC-4C-cis can be converted into highly active Azo-PROTAC-4C-trans under visible light, thereby initiating protein degradation. Azo-PROTAC-4C-cis can be used for the study of myeloid leukemia.

PROTAC DDa-1 is a multi-targeted DCAF1-recruiting tyrosine kinase PROTAC degrader. PROTAC DDa-1 mediates the degradation of TNK2, CSK, LIMK2, TEC, and BTK, with a DC₅₀ of 90 nM for BTK. PROTAC DDa-1 reduces the viability of BTK-dependent diffuse large B-cell lymphoma cells. PROTAC DDa-1 can be used for the research of diffuse large B-cell lymphoma.

GMB-805 is a BCR-Abl PROTAC degrader with a DC₅₀ of 30 nM in K562 cells. GMB-805 exerts antiproliferative activity in K562 cells. GMB-805 exhibits potent anti-tumor activity with favorable safety profile in vivo. GMB-805 can be used for chronic myeloid leukemia research.

PROTAC BCR-ABL Degrader-2 is a selective Bcr-Abl^T315 PROTAC degrader with a DC₅₀ of 108.7 nM in Ba/F3 Bcr-Abl^T315I cells. PROTAC BCR-ABL Degrader-2 exhibits the most potent degradation efficacy with DR of 69.89% and 94.23% at 100 and 300 nM, respectively. PROTAC BCR-ABL Degrader-2 demonstrates high plasma exposure, and induces significant tumor regression and induces tumor cell apoptosis with a good safety profile in vivo. PROTAC BCR-ABL Degrader-2 can be used for chronic myeloid leukemia (CML) research.

Arg-PEG1-Dasa is a mini-PROTAC targeting BCR-ABL. Arg-PEG1-Dasa induces BCR-ABL degradation (EC₅₀ = 0.85 nM) and shows antiproliferative activity in K562 cells (IC₅₀ = 0.36 nM). Arg-PEG1-Dasa can be used for chronic myeloid leukemia research.

Lys-PEG1-Dasa is a BCR-ABL PROTAC degrader with an DC₅₀ of 0.98 nM in K562 cells. Lys-PEG1-Dasa exerts growth inhibitory with IC₅₀ of 0.4569 nM in K562 cells. Lys-PEG1-Dasa can be used for chronic myeloid leukemia research.

P19As is a BCR-ABL PROTAC degrader based on Asciminib (HY-104010), with a DC₅₀ value of approximately 200 nM for the wild-type BCR-ABL protein. P19As can degrade the T315I mutant and exhibits potent anti-proliferative activity in BaF3-BCR-ABL (T315I) cells. P19As can be used for the study of chronic myeloid leukemia and acute lymphoblastic leukemia.

P19P is a BCR-ABL PROTAC degrader based on Ponatinib (HY-12047), with a DC₅₀ value of approximately 20 nM for the wild-type BCR-ABL protein. P19P can effectively degrade various drug-resistant mutants such as T315I, E255K, H396R, and V468F, and exhibits potent anti-proliferative activity in BaF3-BCR-ABL (T315I) cells. P19P maintains strong inhibitory activity against ABL (T315I), with a IC₅₀ of 13.1 nM. P19P does not inhibit the formation of vascular lumens in HUVEC. P19P can be used for research on chronic myeloid leukemia and acute lymphoblastic leukemia.

SIAIS100 is a potent BCR-ABL PROTAC degrader with an DC₅₀ value of 2.7 nM. SIAIS100 can be used to research chronic myeloid leukemia (CML).

MRT-7612 (Compound 4) is a cereblon-based tyrosine kinases molecular glue degrader. MRT-7612 significantly induces HCK and LYN degradation, with week efficacy on LCK. MRT-7612 can be used for cancers like chronic myeloid leukemia, autoimmune and chronic inflammatory diseases research.

SIAIS056 is a BCR-ABL PROTAC degrader with a DC₅₀ value of 0.18 nM. SIAIS056 time-dependently inhibits the BCR-ABL signaling pathway, accompanied by decreased phosphorylation of BCR-ABL and the downstream molecules STAT5 and CRKL in K562 cells. SIAIS056 induces the degradation of several clinically relevant resistance-conferring mutations of BCR-ABL. SIAIS056 exhibits anti-proliferative activity and induces substantial tumor regression in K562 xenograft models. SIAIS056 can be used for leukemia research.

SJ11646 is a Dasatinib (HY-10181)-based LCK PROTAC degrader with a DC₅₀ of 0.00838 pM. SJ11646 has potent cytotoxicity against LCK-activated T-cell acute lymphoblastic leukemia (T-ALL) cells and primary leukemia samples with drastically prolonged suppression of LCK signaling, and induces T-ALL apoptosis. SJ11646 binds to 51 human kinases with a high affinity (particularly ABL1, KIT, and DDR1). SJ11646 has superior antileukemic efficacy in T-ALL mice model. . Pink: LCK ligand (HY-107447); Blue: CRBN ligase ligand (HY-163169); Black: linker (HY-76667)