usp1

USP1-IN-2 is a potent USP1 inhibitor with potential anti-tumor activity for the study of cancer.

SJB3-019A is a potent, potent and novel ubiquitin-specific protease 1 (USP1) inhibitor, which promotes ID1 degradation and cytotoxicity in K562 cells 5 times more than SJB2-043, with IC50 of 0.0781 μM. SJB3-019A inhibits cell proliferation and causes cell apoptosis.

C527 is a potent pan DUB enzyme inhibitor with a high affinity for the USP1/UAF1 complex (IC50=0.88 μM).

KSQ-4279 (USP1-IN-1) is a dual USP1/PARP inhibitor, a potent and selective PARP inhibitor with anti-cancer activity, used for research in non-small cell lung cancer and various other cancers.

ML323 is a reversible and effective USP1-UAF1 inhibitor in a Ub-Rho assay (IC50: 76 nM) and in orthogonal gel-based assays using K63-linked diubiquitin (di-Ub) (IC50: 174 nM 820 nM)and monoubiquitinated PCNA (Ub-PCNA) (IC50: 820 nM) as substrates, respectively.

I-138 is an orally active and potent reversible inhibitor of USP1-UAF1.I-138 induces mono-ubiquitination of FANCD2 and PCNA and inhibits USP1 auto-cleavage in cells.

SJB2-043, an inhibitor of USP1-UAF1, has an IC50 of 544 nM.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It promotes the activation of the DDR (DNA damage repair) pathway, inducing cell cycle arrest and apoptosis, thereby inhibiting cell viability. USP1-IN-11 increases the sensitivity of cells resistant to Olaparib and shows synergistic effects with Andrographolide in cancer cells with normal BRCA function. In the MDA-MB-436 xenograft model, USP1-IN-11 exhibits a significant dose-dependent antitumor effect.

USP1-IN-9 (Compound 1m) is a reversible and non-competitive inhibitor of ubiquitin-specific protease (USP1) with an IC50 value of 8.8 nM. It is synthesized based on the structures of ML323 and KSQ-4279 as a pyrido[2,3-d]pyrimidin-7(8H)-one derivative. USP1-IN-9 exhibits excellent inhibition of USP1/UAF and demonstrates strong antiproliferative effects on breast cancer cells. When combined with the PARP inhibitor olaparib, USP1-IN-9 enhances the cytotoxic effect on MDA-MB-436/OP cells. USP1-IN-9 holds potential for research in the field of cancer.

USP1-IN-13 (compound 2) is a potent, orally active inhibitor of USP1 with an IC50 value of 0.00102 µM. It effectively suppresses cell colony formation.

USP1-IN-12 (compound 4) is a potent, orally active USP1 inhibitor with an IC50 value of 0.00366 µM. It is capable of inhibiting cell colony formation.

USP1-IN-15 is an orally effective and selective inhibitor of USP1 with an IC50 of 12.3 nM. It demonstrates high specificity towards USP1, with negligible inhibition of off-target deubiquitinating enzymes. USP1-IN-15 blocks cell colony formation, induces S phase arrest, and stabilizes ubiquitinated PCNA. Additionally, USP1-IN-15 exhibits synergistic antiproliferative activity and significantly inhibits tumor growth in vivo. This compound can be utilized for research on BRCA-mutated breast cancer.

USP1-IN-3 is a selective inhibitor of USP1, effectively inhibiting USP1-UAF1 with an IC50 of less than 30 nM. USP1-IN-3 is utilized for cancer research.

USP1-IN-5 (compound 10) is a potent inhibitor of USP1, with an IC50 of less than 50 nM, and of MDA-MB-436 cells, exhibiting an IC50 of less than 50 nM [1].

USP1-IN-6 (Compound 11) functions as a potent USP1 inhibitor, exhibiting an IC50 value of less than 50 nM. Additionally, it demonstrates inhibitory activity against MDA-MB-436 cells with a comparable IC50. [1]

USP1-IN-4 (compound 10) serves as a potent inhibitor of USP1, exhibiting an IC 50 of 2.44 nM. It demonstrates anticancer properties and operates synergistically with various anticancer drugs [1].

USP1-IN-7 (Compound 3), a potent inhibitor of ubiquitin specific peptidase 1 (USP1) and its cofactor UAF1, exhibits an inhibition concentration (IC 50) of ≤50 nM. It also effectively inhibits the proliferation of MDA-MB-436 cells at similar concentrations [1].

USP1-IN-10 (compound 2) is an effective tricyclic USP1 inhibitor with an IC50 of 7.6 nM. It inhibits the viability of MDA-MB-436 cells with an IC50 of 21.58 nM, demonstrating potential for use in cancer research.

USP15-IN-1 is a potent USP15 inhibitor (IC50 is 3.76 μM) with high antiproliferative activity against non-small cell lung cancer and leukemia cells. As an interacting protein of cGAS, USP15 promotes cGAS to recognize DNA and activate downstream signaling pathways.

USP10-IN-3 (compound D1) is a potent inhibitor of USP10, with an IC50 of 7.2 µM. It can suppress cell proliferation, induce apoptosis, and cause cell cycle arrest in the S phase.

USP10-IN-4 is a potent inhibitor of ubiquitin-specific protease 10 (USP10), with an IC50 of 10.87 μM and a Kd of 365 nM. It effectively inhibits USP10-mediated proteasomal degradation of downstream proteins YAP and p53, leading to the downregulation of CDK4 in the p53 signaling pathway. USP10-IN-4 promotes apoptosis in liver cancer cells (apoptosis) and inhibits the initiation and progression of liver cancer. It is applicable in the study of hepatocellular carcinoma (HCC).

USP11-IN-1 (Compound 26) is a selective inhibitor of ubiquitin-specific protease 11 (USP11) with an IC50 value of 10.9 μM. It displays IC50 values of 18.1 μM for USP4 and greater than 500 μM for USP15, with a selectivity index (SI) of 1.7 and more than 100, respectively. USP11-IN-1 demonstrates significant antiproliferative activity against PEO4 and MDA-MB-231 cells, with IC50 values of 0.47 μM and 6.5 μM, while exhibiting lower cytotoxicity towards MRC-5 cells (IC50 greater than 10 μM). This compound is applicable in the study of USP11-related malignancies.

IU1-47 is an effective and specific USP14 inhibitor (IC50: 0.6 μM). IU1-47 causes tau elimination in cultured neurons. IU1-47 inhibits IsoT/USP5 (IC50: 20 μM).

Spautin-1 is an autophagy inhibitor that suppresses the deubiquitination activity of ubiquitin-specific peptidase USP10 and USP13. Spautin-1 inhibits UPR and exhibits preferential cytotoxicity in glucose-starved cancer cells.