Histone Acetyltransferase Degrader

(R,R)-dWIZ-1 is the (R,R) enantiomer of dWIZ-1 (HY-159098). dWIZ-1 is a potent WIZ molecular glue degrader. (R,R)-dWIZ-1 can be used in studies related to sickle cell disease and β-thalassemia.

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.

NP1192 is a potent, selective PROTAC NAT10 degrader. NP1192 promotes NAT10 ubiquitination and degradation. NP1192 inhibits ac4C modification. NP1192 demonstrates dual inhibition of hypoxia-driven glycolysis and immunosuppression via NAT10/HIF-1α/PD-L1 axis disruption, achieving superior antitumor efficacy and synergizing with anti-PD-L1 both in vitro and in vivo. NP1192 can be used for ovarian, cervical, and glioblastoma cancer research.

PROTAC KAT2A/B degrader-1 is an orally active CRBN-baed histone acetyltransferase KAT2A/KAT2B PROTAC degrader. PROTAC KAT2A/B degrader-1 induces degradation of KAT2A and KAT2B proteins. PROTAC KAT2A/B degrader-1 inhibits proliferation of acute myeloid leukemia and small cell lung cancer cells. PROTAC KAT2A/B degrader-1 can be used for the research of acute myeloid leukemia, small cell lung cance.

PROTAC p300 degrader-1 is a paralog-selective, PROTAC-based degrader targeting the p300/CBP protein. It exhibits potent antiproliferative, cell cycle arrest and pro-apoptotic activities, and can be used in the research and development of antitumor drugs and related mechanism studies for hematological malignancies (AML, MM, NHL).

GSK702, a PROTAC, is a the less active cis-(S,S)-enantiomer of GSK983 (P300/CBP-associated factor (PCAF)/general control nonderepressible 5 (GCN5) PROTAC). GSK702 induces only a small decrease of PCAF protein levels. GSK702 binds to CRBN and causes a reduction of IL-1β in macrophages. GSK702 can be used for the study of inflammatory mediators.

KAT2A degrader-1 is a molecular glue degrader targeting KAT2A, with a DC₅₀ of 89 nM in Kelly cells. KAT2A degrader-1 recruits KAT2A to cereblon (CRBN) in a degron-independent manner, forms a ternary complex with KAT2A and CRBN, and drives the polyubiquitination and proteasome-dependent degradation of KAT2A. KAT2A degrader-1 reduces the level of histone H3 lysine 9 acetylation (H3K9Ac). KAT2A degrader-1 induces antiproliferative effects in acute myeloid leukemia cells, while enhancing KAT2A-CRBN dimerization activity and eliminating the targeting effect on GSPT1. KAT2A degrader-1 can be used for research related to acute myeloid leukemia.

PROTAC CBP/EP300 Degrader-5 is a CBP and EP300 PROTAC degrader. PROTAC CBP/EP300 Degrader-5 relies on the ubiquitin-proteasome pathway to preferentially induce ubiquitination and degradation of EP300 rather than CBP. PROTAC CBP/EP300 Degrader-5 induces G1 phase cell cycle arrest and triggers Apoptosis. PROTAC CBP/EP300 Degrader-5 is applicable to research related to EP300-dependent malignant tumors.

XYD198 (Compound 14h) is an orally active degrader for CBP/p300. XYD198 inhibits CBP/p300 bromodomain with IC₅₀ of 213.5 nM. XYD198 exhibits antitumor activity against acute myeloid leukemia.

dCBP-30 is an orally active, selective and dual-acting CBP/p300 PROTAC degrader with DC₅₀ values of 0.05 nM (CBP) and 0.04 nM (p300), respectively. dCBP-30 reduces the acetylation levels of histone substrates H3K27, H3K18, H2BK5 and H2BK20, downregulates multiple myeloma-specific dependency programs, and induces multiple myeloma cell apoptosis. dCBP-30 triggers tumor regression and prolongs survival in multiple myeloma xenograft mouse models, and exhibits synergistic antiproliferative activity with dexamethasone. dCBP-30 can be used for the research of multiple myeloma.

XYD129 is a CBP/p300 PROTAC degrader. XYD129 potently binds to CBP, p300 and CRBN proteins, with IC₅₀ values of 0.021 μM, 0.03 μM and 0.18 μM, respectively. XYD129 forms a ternary CRBN-CBP/p300 complex and induces CBP/p300 degradation via the ubiquitin-proteasome system. XYD129 inhibits tumor growth and suppresses the proliferation of acute myeloid leukemia cells. XYD129 can be used in studies related to acute myeloid leukemia.

KAT2A degrader-2 is a selective molecular glue degrader targeting KAT2A, with a DC₅₀ of 22 nM in Kelly cells. KAT2A degrader-2 acts as a molecular glue to recruit KAT2A to CRBN, forming a ternary complex that drives the polyubiquitination and proteasome-dependent degradation of KAT2A. KAT2A degrader-2 reduces the acetylation level of histone H₃ lysine 9 via the ubiquitin-like and proteasome-dependent pathway. KAT2A degrader-2 can be used for the research of acute myeloid leukemia.

CBP/p300 ligand 10 (Compound 3-E) is a CBP/p300 degrader. CBP/p300 ligand 10 also serves as a PROTAC target protein ligand (Ligands for Target Protein for PROTACs) and can be used to synthesize the PROTAC CBP/p300 Degrader-2 (HY-181261).

WIZ degrader 3 (Compound 29) is a molecular glue degrader for widely interspaced zinc finger motifs (WIZ), with an AC₅₀ of 6.4 nM. WIZ degrader 3 induces the expression of fetal hemoglobin (HbF), with an EC₅₀ of 45 nM. WIZ degrader 3 can be used for the research of blood disorders, such as sickle cell disease and β- thalassemia.

Pomalidomide-NH-PEG6-amide-C2-CPI-1612 is a CBP/EP300 PROTAC degrader with a DC₅₀ value of 1.3 μM. Pomalidomide-NH-PEG6-amide-C2-CPI-1612 mediates the formation of a ternary complex between CRBN and the core of CBP, with an EC₅₀ of 1.2 μM. Pomalidomide-NH-PEG6-amide-C2-CPI-1612 inhibits cancer cell growth and exhibits cell line-specific degradation activity. Pomalidomide-NH-PEG6-amide-C2-CPI-1612 can be used in research related to multiple myeloma and leukemia.

PROTAC MLT Degrader 1 is a heterobifunctional degrader of p300 protein PROTAC based on MLT. PROTAC MLT Degrader 1 significantly reduces the intracellular protein level of p300. PROTAC MLT Degrader 1 can be used in Alzheimer's disease research.

WIZ degrader 7 (Example 16) is a WIZ molecular glue degrader with an IC₅₀ value of < 0.01 μM. WIZ degrader 7 can be used to investigate sickle cell disease (SCD) and thalassemia.

WIZ degrader 6 (compound 10) is a WIZ molecular glue degrader with the EC₅₀ of <0.01 μM. WIZ degrader 6 can be used for study of sickle cell disease.

WIZ degrader 5 (example 41) is a molecular glue degrader for widely interspaced zinc (WIZ) finger motifs with an AC₅₀ of 0.14 nM. WIZ degrader 5 induces the expression of fetal hemoglobin (HbF) with an EC₅₀ of 25 nM. WIZ degrader 5 can be used in research related to hereditary blood disorders, such as sickle cell disease (SCD) and thalassemia.