BRD4 Inhibitor

BD-IN-1 is a pan bromodomain (BD) inhibitor with K_D values of 250, 420, 130, 430, 67, 240, 970 nM for BRD4(1), CBP, BRPF1B, BRD7, BRD9, BRDT(1), CECR2 respectively. BD-IN-1 shows antiproliferative activity.

BRD4 Inhibitor-12 (Compound 9) is a BRD4 ligand, and can be used for research of cancer, infammation.

GW 841819X is a benzodiazepine inhibitor of bromodomains of the BET family (BRD2, BRD3, BRD4) that inhibits the binding of Diazepam to central GABA receptors. GW 841819X can be used in the research of BET bromodomain-related diseases, such as cancer.

WNY0824 (PLK1/BRD4-IN-1) is an orally active dual inhibitor of PLK1 and BET protein families, with IC₅₀ values ​​of 22, 402.5, 150.7, 103.9, and 311.9 nmol/L for PLK1, BRD2, BRD3, BRD4, and BRDT, respectively. WNY0824 induces cell cycle arrest and apoptosis by inhibiting AR- and MYC-mediated transcriptional processes. In addition, WNY0824 also inhibits tumor growth in Enzalutamide (HY-70002) resistant CRPC xenograft tumor models.

LCI40 is an orally active dual PI3K/BRD4 inhibitor (PI3Kα IC₅₀ = 0.071 μM, PI3Kβ IC_{50 =} 0.17 μM, PI3Kγ IC₅₀ = 0.66 μM, PI3Kδ IC₅₀ = 0.072 μM, BRD4 BD1 IC₅₀ = 0.19 μM, and BRD4 BD2 IC₅₀ = 1.88 μM. LCI40 inhibits phosphorylation of pAKT (S473) and suppresses c-MYC levels in mantle cell lymphoma cells. LCI40 displays immunomodulatory capacity with minimal toxicity to normal mouse immune cells. LCI40 can be used for the research of mantle cell lymphoma.

PROTAC BRD4 Degrader-14 is a PROTAC-type BRD4 degrader, which is predicted to be a weak VHL binder and an inactive BRD4 degrader.

BRD4-IN-42 is a BRD4 BD1 inhibitor with an IC₅₀ of 108.50 nM. BRD4-IN-42 can be used for the synthesis of PROTACs and serves as the target protein moiety of PROTAC BET Degrader-18 (HY-184335). BRD4-IN-42 inhibits the proliferation of wild-type and SHP099-resistant acute myeloid leukemia cells. BRD4-IN-42 is applicable to research related to acute myeloid leukemia.

CK2-TN03 is an ATP-competitive casein kinase 2 (CK2) inhibitor, with an IC₅₀ of 165 nM and a K_i of 20 nM. CK2-TN03 inhibits CK2-mediated survivin activation and reduces CK2-dependent phosphorylation levels of BRD4/MYCN and AKT1. CK2-TN03 exerts anti-neuroblastoma effects by inhibiting survivin, leading to mitotic catastrophe and apoptosis of cancer cells. CK2-TN03 can be used in studies related to neuroblastoma.

DW34 is an orally active pan-BRD4-D1 biased inhibitor with additional BRD4-D2 inhibitive activity. DW34 displays comparable inhibitive efficacy to I-BET151 (HY-13235) (EC₅₀ = 0.16 μM) with low nanomolar EC₅₀ values of 0.14 μM. DW34 significantly reduces liver inflammation induced by LPS (HY-D1056) and APAP (HY-66005) via reducing chemokine expression and cellular necrosis.

CN427 is a quinazoline-based BRD4 inhibitor with a K_d of 66 nM for BRD4. CN427 is applicable to the research of leukemia.

NB512 (compound 39a) is a dual inhibitor for BET and HDAC, which exhibits a efficient binding affinity with BRD4 bromodomains and HDAC1/2, with EC₅₀s of 100-400 nM. NB512 exhibits an anti-proliferative activity towards cancer cells PaTu8988T and NMC.

SJ1461 is a potent and orally active BET inhibitor. SJ1461 inhibits BRD2 (BD1), and BRD2 (BD2), BRD4 (BD1), and BRD4 (BD2) with IC₅₀ values of 1.6 nM, 0.1 nM, 6.5 nM, and 0.2 nM, respectively.

PROTAC BRD4 Degrader-15 is a BRD4 PROTAC degrader with a DC₅₀ of 2.1 nM. PROTAC BRD4 Degrader-15 forms a ternary complex with BRD4 and VHL ubiquitin ligase to induce degradation. PROTAC BRD4 Degrader-15 inhibits the transcription level of the MYC gene. PROTAC BRD4 Degrader-15 suppresses human megakaryocytopoiesis and exhibits antigen-dependent tumor growth inhibition in xenograft models of prostate cancer and acute myeloid leukemia. PROTAC BRD4 Degrader-15 can be used in studies related to prostate cancer and acute myeloid leukemia.

BRD4 D1-IN-2 (compound 26) is a potent and selective BRD4 D1 inhibitor (IC₅₀<0.092 µM). BRD4 D1-IN-2 has 15 nM affinity against BRD4 D1 and over 500-fold selectivity against BRD2 D1 and BRD4 D2 via ITC.

(S)-GNE-987 is an isomer of GNE-987 (HY-129937A), which loses VHL binding capacity and BRD4 protein degradation activity, but retains BRD4 inhibitory activity. (S)-GNE-987 is a BRD4/BET inhibitor that potently binds to the BD1 and BD2 bromodomains of BRD4, with a BRD4 BD1 IC₅₀ of 4.0 nM and a BRD4 BD2 IC₅₀ of 3.9 nM. (S)-GNE-987 inhibits MYC expression and exhibits inhibitory activity against acute myeloid leukemia cells, whereas its CLL1‑6 antibody-drug conjugate shows almost no in vivo antitumor efficacy in the HL‑60 xenograft tumor model. (S)-GNE-987 can be used in related research on acute myeloid leukemia.

PARP1/BRD4-IN-3 (compound HF4) is a potent BRD4 and PARP1 inhibitor with IC₅₀ values of 1210, 2019 nM for BRD4, PARP1, respectively. PARP1/BRD4-IN-3 shows antiproliferative activities. PARP1/BRD4-IN-3 induces apoptosis and cell cycle arrest at G0/G1 phase. PARP1/BRD4-IN-3 causes DNA damage and reduces the protein expression of Rad51. PARP1/BRD4-IN-3 shows antitumor efficacy.

BRD4-IN-5 (example 51) is a BRD4 inhibitor. The K_i values of the two BRD4 domains BDI_K57-E168 and BDII_E352-M457 are 9.7 nM and 16.1 nM, respectively. BRD4-IN-5 can be used in cancer research.

IL-6/RIPK3-IN-1 is an inhibitor of IL-6, RIPK3 and BRD4, with IC₅₀ values of 0.22, 1.32 and 5.91 μM, respectively. IL-6/RIPK3-IN-1 can be used in studies related to inflammation and tissue damage.

BRD4 ligand 14 (Compound Y47) is a BRD4 inhibitor. BRD4 ligand 14 exhibits mild anticancer properties against acute myeloid leukemia by inhibiting BRD4. BRD4 ligand 14 can also be used as a ligand for target protein for PROTAC in the development and design of PROTAC BRD4 degraders, such as PROTAC BRD4 Degrader-42 (HY-180150).

Penipanoid C (Compound 9) is a BRD4 inhibitor. Penipanoid C can be isolated from marine sediment-derived fungus Penicillium paneum SD-44. Penipanoid C has anti-inflammatory activity and cytotoxic activity against the SMMC-7721 cells. Penipanoid C can be used for inflammatory diseases research.