Histone Acetyltransferase Degrader

dCBP-1 is a potent and selective heterobifunctional degrader of p300/CBP based on Cereblon ligand. dCBP-1 is exceptionally potent at killing multiple myeloma cells and ablates oncogenic enhancer activity driving MYC expression.

PROTAC CBP/P300 Degrader-1 is a potent PROTAC CBP/P300 degrader. PROTAC CBP/P300 Degrader-1 potently inhibited cell viability of multiple cancer cell lines.

CBPD-409 is an orally active PROTAC degrader for CBP/p300, with DC₅₀ of 0.2–0.4 nM. CBPD-409 exhibits antiproliferative effects in AR+ prostate cancer cell lines VCaP, LNCaP and 22Rv1, with IC₅₀s of 1.2–2.0 nM. CBPD-409 exhibits antitumor efficacy (Red: CBP inhibitor GNE049 (HY-108435); Blue: CRBN/cullin 4A Thalidomide (HY-14658); Black: Linker).

WIZ degrader 9 is an orally active molecular glue degrader of the WIZ transcription factor. As a molecular glue, WIZ degrader 9 recruits WIZ to the cereblon E3 ubiquitin ligase complex via its ZF7 domain, driving proteasome-dependent degradation of WIZ. WIZ degrader 9 induces hemoglobin production, reduces the level of H3K9 dimethylation across the whole genome and at the β-globin locus, upregulates the transcription of γ-globin and BGLT3, and increases the level of histone H3K9 acetylation in the promoter region of HBG1/2. WIZ degrader 9 effectively induces fetal hemoglobin production in both mice and cynomolgus monkeys. WIZ degrader 9 can be used for research on sickle cell disease.

BMS-986470, a HbF-activating CRBN E3 ligase modulator (CELMoD), is an orally active dual molecular glue degrader targeting ZBTB7A and WIZ. BMS-986470 has potent γ-globin induction activity. BMS-986470 can be used for sickle cell disease (SCD) research.

JET-209 is a potent CBP/p300 PROTAC degrader, with DC₅₀ values of 0.05 nM and 0.2 nM for CBP and p300. JET-209 demonstrates remarkable anti-tumor activity against various acute leukemia cell lines and effectively inhibits tumor growth in xenograft tumor models. JET-209 can be used for the study of acute leukemia.

CBPD-268 is a potent and orally active CBP/p300 PROTAC degrader with an DC₅₀ value of ≤ 0.03 nM. CBPD-268 induces CBP/p300 degradation and inhibits cell growth. CBPD-268 shows antitumor activity. CBPD-268 has the potential for the research of AR-positive prostate cancer (Structure Note: Red, Androgen receptor degrader (HY-W248665A); Blue, CBP/p300 ligand (HY-161483); Black, Linker).

GSK699 is a KAT2A/B/PCAF/GCN5 PROTAC degrader. GSK699 induces proteasome-dependent degradation of KAT2A, KAT2B, PCAF and GCN5, regulates the histone acetyltransferase activity of the SAGA complex, and reduces the level of histone H3K9ac. GSK699 inhibits the growth of neuroblastoma, acute myeloid leukemia and small cell lung cancer cells. GSK699 reduces the production of inflammatory cytokines and chemokines, and impairs LPS-stimulated immune cell responses. GSK699 is applicable to research related to acute myeloid leukemia, small cell lung cancer, neuroblastoma and inflammatory diseases.

WIZ degrader 8 (TFA) is the trifluoroacetic acid of WIZ degrader 8 (HY-169955). WIZ degrader 8 (compound 10) is a potent and selective degrader of the transcription factor WIZ, which can potently induce HbF expression. WIZ degrader 8 can lead to WIZ degradation and induce HbF expression, and has the potential to be an inhibitor of sickle cell disease.

dWIZ-1 is an orally active molecular glue and chemical probe targeting the WIZ transcription factor, which based on an IMiD backbone, binding to human WIZ with an affinity of 3.5 μM. dWIZ-1 recruits WIZ to the cereblon-DDB1 complex via its ZF7 domain, thereby triggering proteasome-dependent degradation of WIZ. dWIZ-1 significantly induces fetal hemoglobin expression in erythroblasts while reducing the level of inhibitory H3K9 dimethylation at WIZ binding sites such as the β-globin locus. Meanwhile, dWIZ-1 does not affect the proliferation and differentiation of erythroblasts, and no cytotoxicity is observed in in vitro cells or cynomolgus monkey models. dWIZ-1 serves as a critical tool molecule for investigating the mechanism and underlying pathways of sickle cell disease.

WIZ degrader 8 (compound 10) is a potent and selective degrader of the transcription factor WIZ, which can potently induce HbF expression. WIZ degrader 8 can lead to WIZ degradation and induce HbF expression, and has the potential to be an inhibitor of sickle cell disease.

QC-182 is a p300/CBP PROTAC degrader with a DC₅₀ of 93 nM against p300. QC-182 induces ubiquitination and proteasomal degradation of p300 and CBP in a CRBN-dependent manner. QC-182 induces Apoptosis. QC-182 exhibits anticancer activity against liver cancer cells. QC-182 can be used for the research of hepatocellular carcinoma.

PROTAC CBP/P300 Degrader-3 (P-007) is a PROTAC-based CBP and p300 degrader (extracted from patent WO2020173440).

MJP6412 is a p300 and CBP PROTAC degrader that potently degrades p300 and CBP in 22Rv1 cells with DC₅₀ values of 1.6 nM and 1.2 nM, respectively. MJP6412 downregulates the expression of AR-FL, AR-V7 and c-MYC, as well as androgen receptor target genes (KLK3, FKBP5, TMPRSS2). MJP6412 completely abolishes p300/CBP-dependent histone acetylation (H3K27Ac and H2BNTAC) and induces G₁ cell cycle arrest. MJP6412 inhibits cancer cell proliferation and tumor growth. MJP6412 can be used in prostate cancer-related research.

WIZ degrader 4 (Example 1) is a WIZ degrader with an AC₅₀ value of 160 nM. WIZ degrader 4 can be used to investigate sickle cell disease (SCD) and thalassemia.

PROTAC KAT6 Degrader-2 is a KAT6A PROTAC degrader. PROTAC KAT6 Degrader-2 induces ubiquitination and proteasomal degradation of KAT6A. PROTAC KAT6 Degrader-2 exhibits high maximum fold activity in ternary complex formation assays. PROTAC KAT6 Degrader-2 can be used in studies related to breast cancer.

PROTAC KAT6 Degrader-1 is a CRBN-dependented KAT6 PROTAC degrader. PROTAC KAT6 Degrader-1 inhibits cancer cells proliferation.

XYD190 (Compound 14g) is an orally active degrader for CBP/p300. XYD190 inhibits CBP/p300 bromodomain with IC₅₀ of 483.7 nM. XYD190 exhibits antitumor activity against acute myeloid leukemia.

PROTAC CBP/p300/BRD4 Degrader-1 is a dual-target PROTAC degrader with DC₅₀ values of 8.8 pM (BRD4), 6.55 nM (CBP), and 1.05 nM (p300). PROTAC CBP/p300/BRD4 Degrader-1 induces CRBN- and proteasome-dependent degradation of BRD4 and CBP/p300, downregulates c-Myc and acetyl-H3K27, induces apoptosis. PROTAC CBP/p300/BRD4 Degrader-1 acts as an antiproliferative and antitumor agent, induces tumor growth inhibition in xenograft models. PROTAC CBP/p300/BRD4 Degrader-1 can be used for the research of prostate cancer and colorectal cancer.

PROTAC CBP/P300 Degrader-4 is a p300/CBP PROTAC degrader with DC₅₀ of 17.4 nM and 10.2 nM against p300 and CBP in U2OS cells, respectively. PROTAC CBP/P300 Degrader-4 forms ternary complexes with p300 or CBP and an E3 ligase, drives ubiquitination, and mediates proteasomal degradation. PROTAC CBP/P300 Degrader-4 can be used for the research of hematological malignancies.