Histone Acetyltransferase Degrader

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

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.

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.

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.

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.

WIZ degrader 4 is a WIZ molecular glue degrader with an AC₅₀ value of 16 nM. WIZ degrader 4 induces the expression of fetal hemoglobin (HbF) with an EC₅₀ of 47 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.

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.

(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 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).

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.

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.

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.

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.