hiv-in-4

HIV-IN-4 (Compound 12) is a potent inhibitor demonstrating significant anti-HIV activities [1].

HIV-1 protease-IN-4 (Compound II-22), a potent inhibitor of the HIV-1 protease, acts as a prodrug for atazanavir and significantly enhances its bioavailability in rat plasma, achieving a 5-fold increase in the area under the curve (AUC) and a 67-fold increase in concentration at 24 hours (C24) compared to oral administration of atazanavir alone [1].

Apricitabine (SPD754) is a highly selective and orally active HIV-1 reverse transcriptase inhibitor (Ki=0.08 μM), the (-) enantiomer of 2′-deoxy-3′-oxy-4′-thiocytidine (dOTC) . Apricitabine inhibits DNA polymerase α, β and γ with Ki values of 300 μM, 12 μM and 112.25 μM, respectively. Apricitabine has shown good antiretroviral therapeutic efficacy in antiretroviral HIV-infected patients, with good tolerability and low selective resistance.

HIV-1 inhibitor-54 is a potent inhibitor of WT HIV-1 (strain IIIB) in MT-4 cells, demonstrating anti-HIV activity with an EC50 of 32 nM. [HIV-1 inhibitor-54 can be used to study viral infections.]

Gamibetal (4-Amino-3-hydroxybutyric Acid) is used as a chiral reagent in the synthesis of antiepileptic and hypotensive drug GABOB and analogues. Also used in the preparation of HIV-1 inhibitors derived from Betulinic Acid (B330250).

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

IT1t dihydrochloride inhibits CXCL12 CXCR4 interaction with IC50 of 2.1 nM. IT1t dihydrochloride is an antagonist of CXCR4.

4'-Ethynyl-2'-deoxyadenosine (4'-E-dA), a nucleoside reverse transcriptase (RT) inhibitor, demonstrates potent activity against drug-resistant HIV variants, with an EC50 of 98 nM in MT-4 cells for anti-HIV-1 activity.

Mavorixafor trihydrochloride is a selective and orally available CXCR4 antagonist (IC50: 13 nM against CXCR4 125I-SDF binding) and also inhibits the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs (IC50s: 1 and 9 nM).

IT1t inhibits CXCL12 CXCR4 interaction with an IC50 of 2.1 nM. is a potent CXCR4 antagonist.

AMD 3465 also potently inhibits the replication of X4 HIV strains (IC50: 1-10 nM). However, it has no effect on CCR5-using (R5) viruses. AMD 3465 (GENZ-644494) is a potent antagonist of CXCR4, inhibits binding of 12G5 mAb and CXCL12AF647 to CXCR4, with IC

D77 is anti-HIV-1 inhibitor. D77 inhibits HIV-1(IIIB) replication by EC50 value of 23.8 μg/ml in MT-4 cell (5.03 μg/ml for C8166 cells).

Loviride is a non-nucleoside reverse transcriptase inhibitor (IC50: 0.3 µM). Loviride inhibits HIV-1, HIV-2 and SIV replication in MT-4 cells. It is used for reverse transcriptase from HIV-1.

TAK-220 is a selective and orally bioavailable CCR5 antagonist with IC50 values of 3.5 nM for RANTES binding inhibition and 1.4 nM for MIP-1α binding inhibition to CCR5.

Stercobilin hydrochloride (mixture of isomers) is a bile pigment metabolized by intestinal bacteria and also acts as an inhibitor of HIV protease (HIVProtease) with a Ki of 4 μM. This compound can induce pro-inflammatory activity in mouse macrophage RAW264 cells, including the production of TNF-α and IL-1β. Stercobilin hydrochloride (mixture of isomers) is utilized in research on inflammation and viral infections.

Methyl piperazine-2-carboxylate (compound 4) is a potent activator of METTL3 METTL14 WTAP. It enhances the production of HIV-1p24 viral particles and increases the level of N6-methyladenosine in the viral RNA genome.

AMD-070 hydrochloride is a CXCR4 antagonist, is useful for Anti HIV.

3'-Deoxy-4-thiothymidine can moderately active in protecting HIV-induced cytopathogenicity of MT-2 and CEM cells.

ZK 756326 is a selective, non-peptide CCR8 chemokine receptor agonist (IC50: 1.8 μM, in human; 2.6 μM, in mouse). Displays no activity at CCR4 5 and CXCR3 4 and shows higher 28-fold selectivity over 26 other GPCRs (less selective at α2A and 5-HT receptors). Induces chemotaxis and inhibits Env-mediated (HIV) cell-cell fusion.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killingTrypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD50of less than 1 μM in a cell culture assay.1,2The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.1O-11 exhibits essentially no anti-fungal activity when assayed usingC. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.3 1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)

3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003). 3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4 References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003).

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X was a single enantiomer but of undefined chirality at the 4-position of the benzodiazepine ring3. GW841819X and JQ1 were recently discovered that bind to the acetyl-lysine binding pocket of BET bromodomains with Kd ranges from 50 to 370 nM [1]. GW841819X bounded to both the individual BD1 and BD2 domains with affinities of 46 and 52.5 nM, respectively. GW841819X-Brd3 interaction was estimated to be around 70 nM4. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia1. It also potent induced the ApoA1 reporter gene with an EC50 of 440 nM. It had very little effect on LDL-R luciferase activity at the concentrations at which it induces ApoA1 expression, suggesting that the effect is indeed specific3. GW841819X competed directly with GATA1 site for BD1 binding and also specifically blocked the interaction between Brd3 and acetylated GATA14. Recent findings reported that GW841819X are chose as an interest compound to further develop into potential drugs against diseases including cancer, HIV infection and heart disease2.

Boromycin is a boron-containing macrolide antibiotic that has been found in Streptomyces. Boromycin inhibits growth of B. subtilis (MIC = 0.05 μg/ml) and induces efflux of potassium ions from B. subtilis without affecting Na+/K+-ATPase activity. It decreases the synthesis of protein, RNA, and DNA in B. subtilis when used at a concentration of 0.05 μg/ml. It inhibits the growth of B. halodurans (MIC = 10 ng/ml) and inhibits the futalosine pathway of menaquinone synthesis in B. halodurans. Boromycin (3.4 nM) reverses bleomycin-induced cell cycle arrest at the G2 phase in Jurkat cells. It inhibits replication of the HIV-1 strains LAV-1 and RF and the HIV-2 strain LAV-2 in MT-4 cells (IC50s = 0.008, 0.11, and 0.007 μM, respectively). It also inhibits replication of a clinical isolate of HIV-1, strain KK-1, in MT-4 cells and peripheral blood mononuclear cells (PBMCs; IC50s = 0.14 and <0.1 μM, respectively).