lin-2

2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005). 2,5-dimethyl Celecoxib is a derivative of celecoxib that does not inhibit COX-2 (IC50 = >100 μM).1 It does inhibit microsomal prostaglandin E synthase-1 (mPGES-1) in HeLa cells (IC50 = 15.6 μM) and reduces prostaglandin E2 production in HeLa, A549, and HCA-7 cells (IC50s = 0.64, 0.83, and 3.08 μM, respectively).2 It inhibits proliferation of drug-sensitive RPMI8226 and multidrug-resistant 8226 Dox40 multiple myeloma cells, as well as increases the rate of apoptosis when used at concentrations of 20 and 30 μM.3 2,5-dimethyl Celecoxib reduces the expression of survivin, cyclin A, cyclin B, MEK1, and MEK2 in 8226 Dox40 cells. The antiproliferative effect of 2,5-dimethyl celecoxib is independent of mPGES-1 inhibition.2 References1. Zhu, J., Song, X., Lin, H.-P., et al. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents. J. Natl. Cancer Inst. 94(23), 1745-1757 (2002).2. Wobst, I., Schiffmann, S., Birod, K., et al. Dimethylcelecoxib inhibits prostaglandin E2 production. Biochem. Pharmacol. 76(1), 62-69 (2008).3. Kardosh, A., Soriano, N., Liu, Y.-T., et al. Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib. Blood 106(13), 4330-4338 (2005).

Potent equilibrative nucleoside transporter 1 (ENT1) inhibitor (IC50 = 0.43 nM). Inhibits hENT1 and hENT2 uptake of [H3]uridine in K562 cells and K15NTD cells respectively. Lin et al (2011) Design, synthesis, and evaluation of 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate (8MDP-fluor), as a novel equilibrativ Bioconjug.Chem. 22 1221 PMID:21539390 |Lin et al (2007) Synthesis, flow cytometric evaluation, and identification of highly potent dipyrid. analogues as equilibrative nucleoside transporter 1 inhibitors. J.Med.Chem. 50 3906 PMID:17636949

CAY10787 is an oxysterol and a negative allosteric modulator of GABAAreceptors.1,2It reduces GABA-induced currents in HEK cells expressing α1β1γ2or α4β3γ2subunit-containing GABAAreceptors (IC50s = 1.5 and 1 μM, respectively).2CAY10787 (500 nM) reduces GABA-induced depolarization of peptidergic and non-peptidergic nociceptors, C-LTMRs, and cold thermosensors in isolated mouse dorsal root ganglion (DRG) neurons.In vivo, CAY10787 (2, 10, and 50 mg/kg) increases latency to nocifensive behaviors in the hot plate test in mice. 1.Hahn, M., Tang, M., and Subbiah, M.T.Cholest-3,5-dien-7-one formation in peroxidized human plasma as an indicator of lipoprotein cholesterol peroxidation potentialBiochim. Biophys. Acta1255(3)341-343(1995) 2.Niu, C., Leavitt, L.S., Lin, Z., et al.Neuroactive type-A γ-aminobutyric acid receptor allosteric modulator steroids from the hypobranchial gland of marine mollusk, Conus geographusJ. Med. Chem.64(10)7033-7043(2021)

Bottromycin A2is an antibiotic originally isolated fromStreptomyces.1It blocks the binding of aminoacyl-tRNA to the A site of the 50S ribosome, inhibiting protein synthesis.2Bottromycin A2is active against clinical isolates of methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistantEnterococciwith MIC values of 1 and 0.5 μg/ml, respectively. 1.Nakamura, S., Yajima, T., Lin, Y., et al.Isolation and characterization of bottromycins A2, B2, C2J. Antibiot. (Tokyo)20(1)1-5(1967) 2.Gouda, H., Kobayashi, Y., Yamada, T., et al.Three-dimensional solution structure of bottromycin A2: A potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant EnterococciChem. Pharm. Bull. (Tokyo)60(2)169-171(2012)

Pantothenate Kinase Inhibitor (PANKi) is a reversible inhibitor of pantothenate kinase (PanK; IC50s = 70, 92, and 25 nM for PanK1β, PanK2, and PanK3, respectively), the rate-limiting enzyme in the synthesis of coenzyme A .1It binds to the ATP-PanK3 complex with an apparent binding constant of 300 nM and exhibits mixed-type inhibition with respect to ATP and pantothenate. PANKi inhibits CoA biosynthesis in C3A cells (IC50= 0.9 μM) with no effect on cell viability when used at concentrations up to 8 μM. PANKi (5 μM) synergizes with BSO to induce ferroptosis in PANC-1 cells and sensitizes the cells to imidazole ketone erastin-induced ferroptosis.2 1.Sharma, L.K., Leonardi, R., Lin, W., et al.A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinasesJ. Med. Chem.58(3)1563-1568(2015) 2.Badgley, M.A., Kremer, D.M., Maurer, H.C., et al.Cysteine depletion induces pancreatic tumor ferroptosis in miceScience368(6486)85-89(2020)

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

α-Conotoxin ImI is a conotoxin that has been found inC. imperialisand has receptor antagonist and anticancer activities.1It is a peptide antagonist of homomeric α7 nicotinic acetylcholine receptors (nAChRs; IC50= 220 nM). α-Conotoxin ImI is selective for α7 nAChRs over α2β2, α3β2, α4β2, α2β4, α3β4, α4β4, and α1β1γδ subunit-containing nAChRs at 5 μM but does inhibit homomeric α9 nAChRs (IC50= 1,800 nM). Administration of paclitaxel in micelles containing α-conotoxin ImI decreases tumor growth in an MCF-7 mouse xenograft model.2Intracerebroventricular, but not intraperitoneal, administration of α-conotoxin ImI (20 nmol/animal) induces seizures in rats.3 1.Johnson, D.S., Martinez, J., Elgoyhen, A.B., et al.α-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: Preferential inhibition of homomeric α7 and α9 receptorsMol. Pharmacol.48(2)194-199(1995) 2.Mei, D., Lin, Z., Fu, J., et al.The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancerBiomaterials4252-65(2015) 3.McIntosh, J.M., Yoshikami, D., Mahe, E., et al.A nicotinic acetylcholine receptor ligand of unique specificity, α-conotoxin ImIJ. Biol. Chem.269(24)16733-16739(1994)