Enzyme inhibitors

Derquantel is a semi-synthetic paraherquamide analogue prepared by removal of the 2-oxo group in a four-step sequence of N-protection. Derquantel is an effective nematicide, which can act as a nicotinic acetylcholine receptor antagonist agent, causing flaccid paralysis and nematode repellent.

(-)-Parthenolide is a sesquiterpene lactone which occurs naturally in the plant feverfew (Tanacetum parthenium) and also promotes the ubiquitination of MDM2 and activates p53 cellular functions.

Ampicillin Sodium Mixture with Sulbactam Sodium is a β-lactamase inhibitor used to enhance the effectiveness of β-lactam antibiotics.

Methacycline HCl is a tetracycline antibiotic, and also an inhibitor of epithelial-mesenchymal transition (EMT) with IC50 of roughly 5 μM, used to treat various infections. Methacycline is active against a wide range of Gram-positive and Gram-negative organisms.

Alvespimycin (17-DMAG; KOS-1022; NSC 707545) is a potent, water-soluble Hsp90 inhibitor with IC50 of 62 nM. 17-DMAG displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which overexpress Hsp90 client protein Her2, 17-DMAG causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. In combination with vorinostat, 17-DMAG synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. 17-DMAG treatment at 5 mg/kg or 25 mg/kg three times per week significantly reduces tumor growth of TMK-1 xenografts, by reducing vessel area and numbers of proliferating tumor cells in sections. Consistent the inhibition of FAK signaling in vivo, 17-DMAG treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. Administration of 17-DMAG at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model.

A nonselective COX1 and COX2 inhibitor with IC50 of 0.1 μg/mL and 5 μg/mL, respectively.

Simvastatin is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM .

A penicillin derived beta-lactamase inhibitor and antibacterial agent.

Okadaic acid potassium salt, originally derived from marine dinoflagellates, Prorocentrium sp., is a potent, cell permeable inhibitor of serine/threonine protein phosphatases. It inhibits protein phosphatase 1 (IC50 = 3-15 nM) and protein phosphatase 2A (IC50 = 0.1-1 nM).

Zotarolimus (INN, codenamed ABT-578) is an immunosuppressant. It is a semi-synthetic derivative of rapamycin. It was designed for use in stents with phosphorylcholine as a carrier. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology.

Ribavirin is a guanosine (ribonucleic) analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside inhibitor.

Dihydrocytochalasin B, a sort of mycotoxin derivative, has been found to restrain actin polymerization as well as mitosis.

Doxorubicinol is the major metabolite of doxorubicin, which inhibits DNA topoisomerase II by inducing double-stranded DNA breaks.

Fluorouracil (5-Fluoracil, 5-FU) is a DNA/RNA synthesis inhibitor, which interrupts nucleotide synthetic by inhibiting thymidylate synthase (TS).

Sulochrin is a fungal metabolite isolated from Aspergillus and Penicillium. It has anti-allergic, anti-angiogenic and anti-viral activities. It is an anti-angiogenic agent that can inhibit VEGF, thereby inhibiting the capillary-like formation of human umbilical vein endothelial cells. It also inhibits the activation and chemotaxis of eosinophils.

Potent, cell-permeable, IP3-independent intracellular calcium releaser. Blocks the transient increase in intracellular Ca2+ induced by angiostatin and endostatin. Induces apoptosis by disrupting intracellular free Ca2+ levels; incorporated into chemotherapeutic prodrug formulations. In cells, sarco/endoplasmic calcium ATPases (SERCAs) transport free calcium into the sarcoplasmic and endoplasmic reticula, lowering intracellular calcium levels to stop signaling through this cation. Thapsigargin is a non-competitive, cell permeable inhibitor of calcium transport by SERCAs (IC50 values are cell type-dependent and range from ~2-80 nM). Inhibition of SERCAs leads to an increase in intracellular calcium, which has been linked to cell activation, release of histamine from mast cells, and increased proliferation of certain types of cancer cells. In vivo, thapsigargin and related sesquiterpene lactones have anti-inflammatory and anti-cancer effects.

Pentostatin is an adenosine deaminase inhibitor isolated from Streptomyces and effective against cancer cell lines. Pentostatin is a purine nucleoside analog that irreversibly inhibits adenosine deaminase (Ki = 0.9 pM) and thus interrupts DNA synthesis in dividing cells. Pentostatin has been reported to display strong efficacy in the clinical treatment of hairy cell leukemia as well as relapsed chronic lymphocytic leukemia.

A minor component of the zearalenone complex produced by several species of fusarium. Zearalanone is an estrogen receptor agonist (EC50 = 0.11 µM).

Azamulin is an azole derivative of pleuromutilin. Azamulin is a highly selective inhibitor of cytochrome P450 3A4 (CYP3A4).

Triacsin C, originally isolated from Streptomyces sp., is a polyunsaturated fatty acid derivative. It has been found to be an acyl-CoA synthetase inhibitor as well as an effective vasodilator. It selectively inhibits arachidonoyl-CoA synthetase in intact cells and the nonspecific acyl-CoA synthetase in cell sonicates, as well as inhibits neutrophil functions.