Bcl-2 Family Degrader

DT2216 is a potent and selective BCL-XL (Bcl-2 family member) degrader based on PROTAC technology. DT2216 causes effective degradation of BCL-XL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. DT2216 inhibits various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets.

Tambiciclib (GFH009, JSH-009) is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib can be used for AML research.

ML281 is a highly selective inhibitor of serine/threonine kinase 33 (STK33) with an IC₅₀ value of 14 nM. ML281 shows 700-fold selectivity over PKA and 550-fold over AurB. ML281 exerts core mechanism by inhibiting STK33: in small cell lung cancer, ML281 downregulates RPS6/BAD signaling phosphorylation, induces apoptosis, and suppresses proliferation, invasion. ML281 reduces STK33-mediated 4-hydroxyphenylpyruvate dioxygenase (HPD) phosphorylation in tyrosinemia . ML281 is suitable for research on STK33 function, KRAS mutation-related cancers (pancreatic cancer, colon cancer, lung adenocarcinoma, etc.), small cell lung cancer, and tyrosinemia-related damage

PZ671 is a potent Bcl-xL PROTAC degrader with an IC₅₀ of 1.3 nM (MOLT-4 cells) and a DC₅₀ of 0.9 nM (Bcl-xL). PZ671 induces apoptosis in MOLT-4 cells. PZ671 effectively inhibits tumor growth and rapidly reverses transient platelet counts reduction in MOLT-4 xenograft mice. PZ671 can be used for the research of cancer, such as small cell lung cancer (SCLC).

PZ703b is a Bcl-xl PROTAC degrader that induces apoptosis and inhibits cancer cell proliferation. PZ703b can be used for the research of bladder cancer research.

WH244 is a BCL-xL and BCL-2 PROTAC degrader with DC₅₀ values of 0.6 nM and 7.4 nM, and K_d values of 6.14 nM and 3.1 nM, respectively. WH244 kills cancer cells dependent on BCL-xL and BCL-2 for survival. WH244 is applicable to relevant research on leukemia.

XZ338 is a highly selective degrader targeting BCL-XL. XZ338 does not degrade BCL-2. XZ338 inhibits MOLT-4 cells with a IC₅₀ value of 3.7 nM. XZ338 has anti-proliferative activity. XZ338 can be used for anti-cancer study. (Target protein ligand: HY-19741; E3 ligase: HY-112078; linker: HY-172799; E3+liner: HY-172800).

dMCL1-2 is a potent, selective MCL1 PROTAC degrader based on a Cereblon ligand, with a K_D value of 30 nM for binding to MCL1. dMCL1-2 induces ubiquitination and degradation of MCL1. dMCL1-2 degrades MCL1, cleaves Caspase-3, and induces Apoptosis. dMCL1-2 can be used in research related to multiple myeloma.

Tambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research.

PZ703b TFA is a Bcl-xl PROTAC degradation agent that induces apoptosis and inhibits cancer cell proliferation for bladder cancer research.

PROTAC Bcl-2/Bcl-xL Degrader-1 is a Bcl-2/Bcl-xL PROTAC degrader with a DC₅₀ of 11.28 nM against Bcl-xL. PROTAC Bcl-2/Bcl-xL Degrader-1 promotes ubiquitination and degradation of Bcl-2/Bcl-xL. It exhibits anticancer activity against acute lymphoblastic leukemia. PROTAC Bcl-2/Bcl-xL Degrader-1 can be used in the research of BCL-2-mediated or BCL-2-dependent diseases.

EGFR-IN-197 is an EGFR inhibitor with IC₅₀ values of 19.5 nM and 12.0 nM against EGFR^L858R/T790M and EGFR^{L858R/T790M/C797S}, respectively. EGFR-IN-197 arrests the cell cycle of NCI-H1975 cells at the G2/M phase, while inhibiting their proliferation, colony formation and migration; it also inhibits mitochondrial translocation and upregulates mitochondrial H₂S levels. EGFR-IN-197 disrupts anti-apoptotic signaling pathways by regulating apoptosis-related proteins; it induces DNA damage and activates pro-apoptotic pathways to trigger apoptosis. EGFR-IN-197 can be used in studies related to non-small cell lung cancer (NSCLC).

Mcl1 Degrader-1 is an autophagy-targeting chimera (AUTAC) that selectively degrades the Mcl1 protein. Mcl1 Degrader-1 mediates K63 ubiquitination of Mcl1 via TRAF6/UBC13, transports it to autolysosomes for degradation through p62/SQSTM1, and activates Beclin1-dependent autophagy. Mcl1 Degrader-1 can be used in studies related to multiple myeloma and non-small cell lung cancer.

PROTAC BCL-xL/BCL-w Degrader 1 (Compound 44) is a BCL-xL/BCL-w PROTAC degrader. PROTAC BCL-xL/BCL-w Degrader 1 has significant anticancer activity with reduced on-target platelet toxicity . Pink: BCL-xL/BCL-w ligand (HY-10087); Blue: CRBN ligase ligand (HY-163233); Black: linker (HY-Y1230)

BCL-xL ligand 2 is a ligand for BCL-xL. BCL-xL ligand 2 can be conjugated with E3 ligase Ligand (HY-138793) and linker to synthesize Bcl-xL PROTAC degrader PZ671 (HY-174876).

PZ703b hydrochloride is a Bcl-xl PROTAC degrader that induces apoptosis and inhibits cancer cell proliferation. PZ703b hydrochloride can be used for the research of bladder cancer research.

BRD4-IN-12 is a potent and orally active BRD4 inhibitor with an IC₅₀ of 7.9 nM. BRD4-IN-12 downregulates the expression of c-MYC, BCL-2, CDK4 and upregulates p21. BRD4-IN-12 inhibits tumor cell proliferation and promotes apoptosis. BRD4-IN-12 exhibits excellent antitumor effects in the HCT-116 colorectal cancer xenograft model. BRD4-IN-12 can be used for the study of colorectal cancer (CRC).

PROTAC Bcl-xL degrader-4 (Compound 2-38-III) is a Bcl-xL PROTAC degrader. PROTAC Bcl-xL degrader-4 has strong anti-tumor activity against HepG2 cells and HUVEC cells. PROTAC Bcl-xL degrader-4 induces cells apoptosis by decreasing mitochondrial membrane potential and activating the MAPK signaling pathway. PROTAC Bcl-xL degrader-4 significantly inhibits tumor growth in xenograft tumor mouse models.