cyclophilin

1. Ganoderic acid D is one of the major components in Ganoderma triterpenes. 2. Ganoderic acid D treatment for 48h inhibits the proliferation of HeLa human cervical carcinoma cells with an IC(5) value of 17.3 +/- .3 microM.

Cyclophilin inhibitor 1 is an effective and orally bioavailable cyclophilin A inhibitor with a Kd of 5 nM, showing potent anti-HCV activity, and an EC50 for HCV 2a of 98 nM.

Cyclophilin inhibitor 3 (compound 7c), a potent inhibitor of cyclophilin A (CypA), exhibited potent anti-HCV effects with an EC50 value of 4.2 μM.

ZX-J-19J (N-(2,3-Diphenyl-6-quinoxalinyl)octanamide), an inhibitor of Cyclophilin J (CyPJ), demonstrates remarkable inhibition of tumor cell growth, comparable to cyclosporine A but much stronger than 5-fluorouracil.

TMN355 is a potent chemical inhibitor of cyclophilin A and reduces foam cell formation and cytokine secretion,and is used for atherosclerosis.

CypD-IN-6 is a potent inhibitor of Cyclophilin D (CypD/PPIF) that effectively suppresses the PPIase activity of CypD (Ki = 32 nM) and binds to CypD (Kd = 60 nM). It is useful for researching diseases associated with the mitochondrial permeability transition pore (MPTP), such as ischemia-reperfusion injury and acute pancreatitis.

CypD-IN-7 is a potent inhibitor of Cyclophilin D (CypD/PPIF) that effectively suppresses the PPIase activity of CypD (Ki= 2.4 nM) and provides protection against the opening of the mitochondrial permeability transition pore (MPTP). It is applicable for research on pancreatitis.

NIM258 is a potent nonimmunosuppressive cyclophilin inhibitor, with a Kd of 1.2 nM for cyclophilin A, and demonstrates anti-HCV activity with an EC50 of 40 nM. It is applicable in research related to HCV infection.

CRV431 is a novel Pan-Cyclophilin Inhibitor, potently inhibiting all cyclophilin isoforms tested - A, B, D, and G (IC50 values ranged from 1-7 nM).

CypD-IN-3, a potent and subtype-selective cyclophilin D (CypD) inhibitor, exhibits a high affinity for CypD with an IC50 value of 0.01 μM. It is applicable in the research of various conditions, such as oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy, and diabetes [1].

CypD-IN-4 is a potent, subtype-selective cyclophilin D (CypD) inhibitor exhibiting a high affinity for CypD with an IC50 value of 0.057 μM. This compound is utilized in the research of various diseases, such as oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy, and diabetes [1].

CypD-IN-1, a potent and subtype-selective inhibitor targeting cyclophilin E (CypE), demonstrates high affinity with IC50 and Ki values of 0.013 μM and 0.072 μM, respectively. This compound is valuable for research into various conditions, including oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy, and diabetes [1].

Cyclosporin A-Derivative 1 Free base is a crystalline intermediate derived from cyclosporin A. Cyclosporin A is an immunosuppressant that binds to cyclophilin and inhibits calcineurin (IC₅₀ ≈ 0.05–0.1 μM).

Cyclosporin A is a natural product and an active fungal metabolite, classified as a cyclic polypeptide immunosuppressant. It binds to cyclophilin and inhibits the activity of calcineurin (IC₅₀ = 7 nM) as well as CD11a/CD18 adhesion molecules. It is commonly used to induce uremia models.

Zoldonrasib (RMC-9805) is a mutant-selective covalent KRAS G12D inhibitor with oral activity and significant antitumor activity, inducing tumor cell apoptosis in preclinical models of various KRAS-mutant cancers.

RMC-6291 is an orally active, covalent inhibitor of KRAS G12C (ON) that forms a tri-complex within tumor cells between KRAS G12C (ON) and cyclophilin A (CypA), thereby preventing KRAS G12C (ON) from signaling via steric blockade of RAS effector binding and eliciting deep and durable suppression of RAS pathway activity in KRAS G12C tumor models [1].

NIM811 is an orally bioavailable dual inhibitor of mitochondrial permeability transition and cyclophilin.

Alisporivir (Debio-025) is a cyclophilin A inhibitor that disrupts the interaction between CypA and NS5A. It exhibits anti-hepatitis C virus (HCV) activity in vivo and in vitro, inhibits the replication of MERS and SARS coronaviruses, and promotes antigen-specific CD8(+) T cell activation.

ZX-J-19L, an inhibitor of Cyclophilin J (CyPJ) PPIase, demonstrates significant inhibition of tumor cell growth. Its potency is comparable to that of CsA and significantly surpasses that of 5-fluorouracil.

HL001 is an orally active small molecule inhibitor of cyclophilin A (CypA) and a receptor antagonist of lysophosphatidic acid 1 (LPA1). It induces cell cycle arrest and apoptosis in tumor cells via p53. By downregulating G3BP1, HL001 promotes reactive oxygen species production and DNA damage to stabilize p53. It disrupts the interaction between MDM2 and p53-72R in a CypA-dependent manner. HL001 exhibits antitumor activity and can also be used in research on pulmonary fibrosis.

TWH106 is an inhibitor of the cyclophilin (Cyp) enzyme, exhibiting strong affinity for CypA and CypB with dissociation constants (KD) of 53 nM and 139 nM, respectively. It effectively inhibits the replication of HIV and HCV, demonstrating antiviral activity.

CypB-IN-1 (Compound 11) is an inhibitor of cyclophilin B (CypB) with a dissociation constant (Kd) of 12 nM. It is used in research related to metabolic dysfunction-associated steatohepatitis (MASH) and the liver fibrosis diseases it induces.

Pan-RAS-IN-5 (compound 7A) is a molecular glue that facilitates the formation of a ternary complex with cyclophilin A (CYPA) and RAS(ON) protein. This complex inhibits the binding of RAF downstream of RAS, demonstrating antitumor activity.

C105SR is a cyclophilin D (CypD) inhibitor targeting peptidyl-prolyl cis-trans isomerase (PPIase). It has an IC50 value of 5 nM for inhibiting mitochondrial permeability transition pore (mPTP) opening. C105SR reduces apoptosis in hepatocytes induced by hypoxia-reoxygenation and boosts calcium retention capacity (CRC). It demonstrates hepatoprotective effects in a mouse model of ischemia-reperfusion injury (IRI).