synergistic effect

Brusatol (NSC-172924) is a natural product isolated from the Brucea javanica plant. It inhibits Nrf2.

Rufigallol (AI3-00865) is an electron-deficient disk-shaped molecule with six hydroxyl groups and is a good unit for inducing the formation of DLC from non-planar AIE molecules, an anthraquinone derivative.Rufigallol induces the acquisition of DLC properties, while the introduction of TPE groups gives the molecular structure good fluorescence in the aggregated state.The remarkable synergistic in vitro antimalarial effect, in vivo with vitamin C and ketones was synergistic and showed antimalarial activity.

JAK3/ BTk-in-2 is a potent JAK3/BTK inhibitor. JAK3/ BTk-in-2 inhibits both BTK and JAK3, which are two important targets IN autoimmune diseases. JAK3/ BTk-in-2 simultaneously inhibits the BTK/JAK3 signaling pathway, showing a synergistic effect. JAK3/ BTk-in-2 has the potential to treat diseases associated with abnormal JAK3 and BTK activity.

JAK3/ BTk-in-1 is a dual JAK3/BTK inhibitor that specifically targets and inhibits Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), two important targets in autoimmune diseases. JAK3/ BTk-in-1 simultaneously inhibited the BTK/JAK3 signaling pathway, showing a synergistic effect. JAK3/ BTK-in-1 is a potential compound for the treatment of immune-related diseases, such as autoimmune diseases, certain types of cancer (including lymphoma and leukemia), and other diseases that may be characterized by an unbalanced immune response.

trans-Cyclohexane-1,2-diol (trans-1,2-Cyclohexanediol) has a synergistic retardation effect on percutaneous absorption and penetration of metronidazole (MTZ).

ZG-2033 (Compound 26) is an orally active HIF-2α agonist that exhibits nanomolar activity (EC50 = 490 nM) in a luciferase reporter assay. It demonstrates an anti-anemic effect and shows synergistic effects with AKB-6548 in anemia, making it useful for the study of renal anemia.

HPK1-IN-54 (Compound 16) is a potent inhibitor of HPK1 (hematopoietic progenitor kinase 1), enhancing T cell activation and proliferation by blocking HPK1 activity to exert antitumor effects. It has an IC50 of 2.67 nM for HPK1, showing excellent selectivity over the MAP4K family (>100-fold) and other selected kinases (>300-fold). HPK1-IN-54 exhibits moderate in vivo clearance and reasonable oral exposure in both mice and rats. Additionally, in the CT26 mouse colon cancer model, HPK1-IN-54 demonstrates significant antitumor activity and shows a synergistic effect when combined with anti-PD-1 therapy. HPK1-IN-54 holds promise for research in the field of immunology.

AKT-IN-24 (Compound M17) is an allosteric inhibitor of AKT exhibiting antitumor activity. In combination with Trametinib, it targets the AKT/mTOR and MEK/ERK signaling pathways while inhibiting epithelial-mesenchymal transition, resulting in a synergistic suppression effect on TNBC. This combination promotes apoptosis and inhibits cell proliferation and migration.

Conteltinibtetrahydrochloride (CT-707 tetrahydrochloride) is the tetrahydrochloride form of Conteltinib. It acts as an inhibitor for FAK (IC50=1.6 nM), ALK, and Pyk2. When used in combination with Cabozantinib, Conteltinib tetrahydrochloride exhibits a synergistic antitumor effect.

JAK-IN-40 (Compound 46) is an inhibitor of JAK, effectively targeting JAK1, JAK2, and JAK3 with IC50 values of 0.022, 0.759, and 1.601 μM, respectively. It reduces the phosphorylation of STAT3 and inhibits the proliferation of cancer cells Ba/F3 and JAK1-TEL Ba/F3 with GI50 values of 0.614 μM and 0.193 μM. JAK-IN-40 arrests cell cycle progression at the G2/M phase in H1975 and H2087 cells, leading to apoptosis. Additionally, JAK-IN-40 exhibits a synergistic anti-tumor effect when used in combination with Osimertinib.

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.

YJZ5118 is a CDK12/13 inhibitor, possessing IC50 values of 39.5 nM and 26.4 nM for CDK12 and CDK13, respectively. This compound can inhibit tumor cell proliferation by inducing DNA damage and apoptosis (Apoptosis) and exhibits a synergistic effect with Akt inhibitors. YJZ5118 is applicable in cancer research.

HQY1428 is an orally active CDK12 inhibitor. It impedes DNA replication, causing cell cycle arrest at the G2/M phase in SKOV3 cells, and induces DNA double-strand breaks as well as apoptosis. In the SKOV3 xenograft mouse model, HQY1428 demonstrates antitumor activity. Additionally, when combined with the HER2 inhibitor Lapatinib in the NCI-N87 xenograft mouse model, HQY1428 produces a synergistic therapeutic effect.

YCH2823 is an inhibitor of USP7 (IC50= 49.6 nM; Kd= 0.117 μM) and demonstrates significant efficacy in suppressing both wild-type TP53 tumors and mutated tumors. It is approximately 5 times more potent than FT671, induces apoptosis, and exhibits a synergistic effect with mTOR inhibitors.

IMPDHII/HDAC1-IN-1 (Compound C12) is an orally active dual inhibitor targeting IMPDHII and HDAC1, with IC50 values of 84.69 nM and 81.75 nM, respectively. It exhibits significant antitumor activity by inhibiting proliferation of K-562 cells (IC50 = 305.31 nM). By simultaneously targeting IMPDHII and HDAC1, this compound demonstrates a synergistic antitumor effect, suppressing tumor cell proliferation and inducing apoptosis. IMPDHII/HDAC1-IN-1 can be utilized in the study of cancers such as chronic myeloid leukemia (CML).

CMP3a is a NEK2 kinase inhibitor. CMP3a efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase E

CGP 43182 is an effective inhibitor of group IIA secretory phospholipase A2 (Group IIA sPLA2) activity in vitro, which can be used to prevent the synergistic effect of pro-inflammatory genes stimulated by cytokines mediated by NFkappaB.

DNA-PK-IN-3 is a highly potent inhibitor of DNA-PK that exerts a synergistic effect with radiotherapy and chemotherapy, enhancing therapeutic outcomes and significantly inhibiting tumor growth. Additionally, it demonstrates remarkable efficacy in reducing damage to normal cells, thereby minimizing adverse side effects, making it a compound of great potential for cancer research applications[1].

JAK3/BTK-IN-5 is a potent inhibitor of JAK3/BTK, crucial targets in autoimmune diseases. Inhibiting the BTK/JAK3 signaling pathway simultaneously has a synergistic effect, enhancing its potential research value for JAK3 kinase and/or BTK-related diseases.

JAK3/BTK-IN-3 is a potent inhibitor of JAK3/BTK and targets two important pathways in autoimmune diseases. The simultaneous inhibition of the BTK/JAK3 signaling pathway exhibits a synergistic effect, highlighting JAK3/BTK-IN-3's potential for investigating JAK3 kinases and/or BTK-related diseases.

JAK3/BTK-IN-4 is a potent inhibitor of JAK3/BTK, targeting critical pathways in autoimmune diseases. The simultaneous inhibition of the BTK/JAK3 signaling pathway exerts a synergistic effect, making JAK3/BTK-IN-4 a promising therapeutic candidate for JAK3 kinase and/or BTK-related diseases.

Ki23057 is a a FGFR2 inhibitor, which enhances the chemosensitivity of drug-resistant gastric cancer cell lines when used in combination with chemotherapeutic drugs. Ki23057 might be therapeutically promising for treating drug-resistant gastric cancer cells, especially when used in combination with SN38, PTX, or VP16. The apoptosis process might be the main mechanism underlying the synergistic effect of these combinations. The ERCC1 and p53 genes may play an integral role in the synergism between Ki23057 and chemotherapeutic agents in drug-resistant cell lines. (source: Cancer Lett. 2011 Aug 1;307(1):47-52).

L0909 is an orally available inhibitors of Hepatitis C virus with a novel mechanism of action (EC50 = 0.022 μM, SI > 600). L0909 could block HCV replication by acting on the HCV entry stage. The high sensitivity to clinical resistant HCV mutants and synergistic effect with clinical drugs were observed for this compound. L0909 as a promising HCV entry inhibitor for single or combinational therapeutic potential.

AS2575959 is a novel GPR40 agonist, exhibiting glucose metabolism improvement and synergistic effect with sitagliptin on insulin and incretin secretion.