Src Degrader

DAS-5-oCRBN is a PROTAC molecule with both c‑Src kinase inhibitory activity and target protein degradation activity, with an EC₅₀ of 45 nM for c‑Src binding. DAS-5-oCRBN binds non-covalently to Cereblon and mediates target protein degradation via the ubiquitin-proteasome pathway. DAS-5-oCRBN can catalytically deplete intracellular c‑Src protein, while blocking both the kinase catalytic function of c‑Src and the non-catalytic protein interactions mediated by its SH2 and SH3 domains. DAS-5-oCRBN inhibits tumor cell proliferation and exerts significant anti-proliferative effects on both c‑Src kinase activity-dependent MDA-MB-231 cells and c‑Src protein level-dependent CAL51 cells. DAS-5-oCRBN can be used in cancer-related research such as studies on triple-negative breast cancer and chronic myeloid leukemia.

DB-3-291 is a CSK-targeting agent with a human CSK K_d of 1 nM and high selectivity for CSK over other kinases bound by dasatinib. DB-3-291 induces targeted degradation of CSK via a ubiquitin-dependent pathway and incorporates dasatinib as the kinase binding ligand. DB-3-291 can be used for the research of innate immune responses to viral DNA.

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.

BLK degrader 1 (compound 9) is a selective degrader of B-lymphoid tyrosine kinase (BLK). BLK degrader 1 shows anticancer activity in several B-lymphoid cell lines.

MRT-10350 (Compound 2) is a cereblon-based HCK molecular glue degrader. MRT-10350 can be used for cancers like chronic myeloid leukemia and HIV-1 infections research.

DB-0646 is a multi-target PROTAC degrader that degrades over 125 distinct kinases in various cell lines, with its degradation process dependent on the activity of p97. DB-0646 induces ubiquitination and degradation of GCK, BUB1 and YES1.

DB0662 is a multi-target kinase-directed PROTAC degrader, targeting kinases including PTK2B, MAPK9, BLK, CSK, LIMK1, etc.

SJ45566 a potent and orally active PROTAC-based LCK degrader, with a DC₅₀ of 1.21 nM. SJ45566 can be used in the research for T‑Cell Acute Lymphoblastic Leukemia.

DFCI-002-06 is an orally active dual-target HCK/BTK PROTAC degrader with DC₅₀ values for HCK and BTK of 1.3 and 4.5 nM respectively. DFCI-002-06 retains higher anti-tumor activity than the HCK/BTK dual-target inhibitor (HY-15805), inducing apoptosis in cancer cells. DFCI-002-06 can be used for the study of MYD88 mutant B-cell malignancies.

LCK degrader-3 (Compound 20) is a CRBN-based LCK molecular glue degrader. LCK degrader-3 can be used in the research of acute lymphoblastic leukemia.

LCK degrader-2 (Compound 17) is a Lck Molecular glue degrader. LCK degrader-2 can be used for cancers like acute lymphoblastic leukemia (ALL) research.

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.

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.

SJ11646 is a LCK PROTAC degrader with a DC₅₀ value of 0.00838 pM against LCK. SJ11646 recruits CRBN and LCK to form a ternary complex, inducing cereblon-mediated proteasomal degradation of LCK. SJ11646 induces cytotoxicity in T-ALL cells, but such cytotoxicity is reduced in cells harboring the LCK^T316I mutation. SJ11646 can be used in studies related to T-cell acute lymphoblastic leukemia.

Lck degrader-1 (Compound 17) is a molecular glue degrader targeting lymphocyte-specific protein tyrosine kinase (LCK) (DC₅₀=23.1 nM). Lck degrader-1 is promising for research of T-cell acute lymphoblastic leukemia (T-ALL).

BY13 is a SRC-3 PROTAC degrader with a DC₅₀ of 0.031 μM. BY13 selectively blocks the ER signaling pathway over that of androgen receptor (AR)) through down-regulating ERα level. BY13 potently overcomes endocrine resistance in breast cancer by inducing cell cycle arrest in G1 phase and apoptosis, with superior effect over Fulvestrant (HY-13636). BY13 significantly inhibits the growth of drug-resistant breast tumors without obvious toxicity in LCC2 xenograft mice model.