olaparib

Olaparib (KU0059436) is a small molecule inhibitor of PARP1/PARP2 (IC50=5/1 nM), with weak inhibitory activity against PARP tankyrase-1 (IC50=1.5 μM), and is selective and orally active. Olaparib exhibits autophagy and mitochondrial autophagy activation activity.

Olaparib-D5 is a deuterium labeled Olaparib. Olaparib (T3015) is a potent and oral inhibitor of PARP.

N-Descyclopropanecarbaldehyde Olaparib suberic acid is a ligand-linker conjugate, utilized in the synthesis of [DDO3602].

N-Descyclopropanecarbaldehyde Olaparib, an Olaparib analogue, incorporates a DOTA moiety. It acts as a CRBN-based ligand for the formation of novel dual EGFR and PARP PROTAC, DP-C-4[1]. N-Descyclopropanecarbaldehyde Olaparib is suitable for radiolabeling with F-18 or a fluorophore to visualize tumors using positron emission tomography (PET) or optical imaging[2].

Olaparib-D5 (Standard) is a reference standard of Olaparib-D5 intended for quantitative analysis, quality control, and related biochemical research applications.

Olaparib impurity 22 is an impurity of Olaparib.

Olaparib-D8 is a deuterated variant of Olaparib. Olaparib (T3015) is an orally active inhibitor of PARP, specifically inhibiting PARP-1 and PARP-2 with IC50 values of 5 nM and 1 nM, respectively. Additionally, Olaparib (T3015) serves as an activator of autophagy and mitophagy.

Olaparib-D4-1 is a deuterated form of Olaparib. Olaparib (T3015) is an orally active PARP inhibitor, with IC50 values of 5 nM and 1 nM for PARP-1 and PARP-2, respectively. Additionally, Olaparib (T3015) acts as an activator of autophagy and mitophagy.

Olaparib (Standard) is a reference standard for research and analysis in studies involving Olaparib. Olaparib (KU0059436) is a small molecule inhibitor of PARP1/PARP2 (IC50=5/1 nM), with weak inhibitory activity against PARP tankyrase-1 (IC50=1.5 μM), and is selective and orally active. Olaparib exhibits autophagy and mitochondrial autophagy activation activity.

Olaparib-[D8] (Standard) is a reference standard of Olaparib-[D8] intended for quantitative analysis, quality control, and related biochemical research applications.

PARPi-FL (PARPiFL) is a fluorescent PARP1 inhibitor used for imaging glioblastoma and detecting oral cancer.

AB25583 is a potent inhibitor of the Polθ helicase domain (Polθ-hel). It blocks MMEJ repair, leading to DNA damage accumulation and synthetic lethality in BRCA1/2-deficient cancer cells.

And1 degrader 1 (Compound A15) is a degrader of acidic nucleoplasmic DNA-binding protein 1 (And1) that notably induces degradation of And1 in NSCLC cells. When combined with Olaparib (1 μM), And1 degrader 1 at a concentration of 5 μM effectively inhibits proliferation in A549 and H460 cells. This compound is applicable in cancer research studies.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It activates the DDR (DNA damage repair) pathway, leading to cell cycle arrest and apoptosis, thereby inhibiting cell survival. USP1-IN-11 increases sensitivity to Olaparib in drug-resistant cells and works synergistically with Andrographolide in cancer cells with functional BRCA. In the MDA-MB-436 xenograft model, USP1-IN-11 demonstrates significant dose-dependent antitumor activity.

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.

BRCA2-RAD51-IN-2 (compound S-35d) is a BRCA2-RAD51 inhibitor that, when combined with 10 µM Olaparib, can inhibit homologous recombination repair.

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.

BER-IN-1 is a base excision repair (BER) inhibitor that specifically targets DNA apurinic/apyrimidinic (abasic) sites. It works by disrupting the BER pathway through β-elimination and β,δ-elimination cleavage at these sites, leading to DNA double-strand breaks (DSBs). BER-IN-1 enhances the effects of the PARP inhibitor Olaparib in cancer cells with normal homologous recombination repair (HR) such as MDA-MB-231, HeLa, and SKOV3. When used in combination with Olaparib, BER-IN-1 can induce S-phase arrest and apoptosis. This compound is utilized in research on cancers, including breast, cervical, and ovarian cancers.

PARP1-IN-44 is a derivative of Olaparib and functions as an orally active PARP1 inhibitor with an IC50 of 0.6 nM. It also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 demonstrates selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. It induces G2/M phase arrest, promotes apoptosis, increases reactive oxygen species (ROS) levels, and disrupts mitochondrial membrane potential. Additionally, PARP1-IN-44 inhibits PARylation and leads to the accumulation of γH2AX. It activates the cGAS-STING pathway, enhancing the expression of IFN-β and CXCL10. In a CT26 tumor mouse model, PARP1-IN-44 enhances CD8+ T cell infiltration, showcasing significant in vivo antitumor activity.

Polθ-IN-9 is an orally active inhibitor of Polθ polymerase with an IC50 of 9.6 nM and a Kd of 47.5 nM. It demonstrates remarkable selectivity, showing no inhibitory activity against other human DNA polymerases, such as Pol α, Pol ε, Pol γ, Pol λ, and Pol μ. In DLD1 BRCA2 KO cells, Polθ-IN-9 exhibits potent antiproliferative activity with an IC50 of 2.9 μM, and it is highly sensitive to MDA-MB-436 cells with an IC50 of 4.9 μM. In MDA-MB-436 xenograft tumor models, the combination of Polθ-IN-9 with Olaparib enhances DNA damage accumulation, increases γH2AX levels, and inhibits tumor growth. Polθ-IN-9 is useful in studying homologous recombination (HR)-deficient cancers such as breast cancer.

ART5537 is a selective EXO1 inhibitor with an EC50 of 55 nM, an IC50 of 3.4 nM, and a Kd of 6.8 nM. It inhibits the homologous recombination (HR) process in HAP1 parental cells with an EC50 of 7.2 nM. The selectivity of ART5537 for the broad-spectrum nuclease superfamily members is over 200-fold higher. Its biological effects are entirely driven by EXO1 inhibition. ART5537 enhances sensitivity to ionizing radiation and exhibits synergism with Olaparib. It is applicable in research on breast and colon cancers.

DN1679 is a potent, selective, and orally active CRBN-dependent dual degrader of CDK12/13 PROTAC. It exhibits DC50 values for CDK12/13 at 8.8/9.8 nM in MDA-MB-231 cells, 5.1/6.4 nM in MDA-MB-157 cells, and 17.2/15.8 nM in MDA-MB-468 cells. DN1679 downregulates mRNA levels of DNA damage response genes such as ATM, ATR, BRCA1, and RAD51. When used in combination with Olaparib, DN1679 shows a significant synergistic anti-tumor effect. It is applicable in research on triple-negative breast cancer.

CAY10760 is a novel RAD51-BRCA2 protein–protein interaction inhibitor (EC₅₀ = 19 μM) that interferes with the homologous recombination process.

PARP1-IN-9 (Compound 5c) is a potent PARP1 inhibitor with an IC50 of 30.51 nM, inducing cell apoptosis and exhibiting superior anticancer activity compared to Olaparib [1].