p 30

UBP 302 is an effective and selective GLUK5-subunit-containing kainate receptor antagonist (apparent Kd=402 nM) and displays very little affinity on GluK2 kainate receptors.

BRK inhibitor P21d hydrochloride is a highly potent inhibitor of breast tumor kinase (BRK PTK6), displaying an IC50 of 30 nM, and effectively suppresses p-SAM68 with an IC50 of 52 nM. This compound serves as a valuable tool for evaluating BRK inhibitors' efficacy in xenograft breast tumor models, enabling in vivo activity assessment.

GP 1a is a potent agonist of cannabinoid receptor 2 (CB2) (EC50=7.1), as shown in cAMP, GTPγS and β-arrestin recruitment assays. GP 1a is approximately 30-fold more selective for CB2 receptors than CB1 receptors and increases P-ERK1/2 expression in HL-60 cells in vitro. GP 1a is beneficial for skin wound healing. GP 1a inhibits inflammation and fibrogenesis while promoting epithelial re-formation.

Pifithrin-α, p-Nitro, Cyclic (PFN-α) is a cell-permeable, active-form inhibitor of p53.

SARS-CoV-IN-2 is an effective inhibitor of SARS-CoV replication.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

MMV024101 is a PI4K inhibitor. MMV024101 exhibits submicromolar potency against P. falciparum NF54 (IC50 =543 nM), low aqueous solubility (<5 μM), and rapid clearance by mouse liver microsomes with only 2% of parent compound remaining after 30 min of incu

o-Iodohippurate sodium is an analogue of p-aminohippuric acid used to determine effective renal plasma flow. Labelled OIH has a higher clearance than other radiopharmaceutical yet developed and is extremely suitable for renography. It is eliminated mainly

β-Defensin-2 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius.2β-Defensin-2 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes.3It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-2 induces IL-31 production by human peripheral blood-derived mast cellsin vitrowhen used at a concentration of 10 μg/ml and by rat mast cellsin vivofollowing a 500 ng intradermal dose.4Expression of β-defensin-2 is increased in psoriatic skin and chronic wounds.5,6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 3.Niyonsaba, F., Ushio, H., Nakano, N., et al.Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokinesJ. Invest. Dermatol.127(3)594-604(2007) 4.Niyonsaba, F., Ushio, H., Hara, M., et al.Antimicrobial peptides human β-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cellsJ. Immunol.184(7)3526-3534(2010) 5.Huh, W.-K., Oono, T., Shirafuji, Y., et al.Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skinJ. Mol. Med. (Berl.)80(10)678-684(2002) 6.Butmarc, J., Yufit, T., Carson, P., et al.Human β-defensin-2 expression is increased in chronic woundsWound Repair Regen.12(4)439-443(2004)

β-Defensin-3 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It inhibits the growth of the periodontopathogenic and cariogenic bacteria F. nucleatum, S. mutans, S. sobrinus, S. salivarius, and L. casei (MICs = 12.5-100 mg/l). It also inhibits the growth of S. aureus, S. pyogenes, P. aeruginosa, E. coli, and C. albicans. β-Defensin-3 stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes when used at a concentration of 30 μg/ml. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 5, and 20 μg/ml, respectively. β-Defensin-3 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose.

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.

6-Prenylindole is a bacterial metabolite that has been found in Streptomyces and has antifungal and antimalarial properties.1 It is active against A. brassicicola strain TP-F0423 and F. oxysporum f. sp. tulipae TU-4-2 (15 and 30 μg/disc in the paper disc assay), and also drug-resistant P. falciparum strain K1 (IC50 = 21 μg/ml).2 |1. Sasaki, T., Igarashi, Y., Ogawa, M., et al. Identification of 6-prenylindole as an antifungal metabolite of Streptomyces sp. TP-A0595 and synthesis and bioactivity of 6-substituted indoles. J. Antibiot. (Tokyo) 55(11), 1009-1012 (2002).|2. Nkunya, M.H., Makangara, J.J., and Jonker, S.A. Prenylindoles from Tanzanian Monodora and Isolona species. Nat. Prod. Res. 18(3), 253-258 (2004).

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).

CC-90005 is a potent, selective, and orally active inhibitor of protein kinase C-θ (PKC-θ) with an IC50 of 8 nM, demonstrating strong selectivity over PKC-δ (IC50=4440 nM). Additionally, CC-90005 can inhibit T cell activation by IL-2 expression[1].

Actinopyrone A is a pyrone isolated from S. pactum with diverse biological activities, showing selective and potent antimicrobial activity against H. pylori (MIC = 0.1 ng mL) and no activity against other Gram-negative bacteria including E. coli, K. pneumoniae, P. aeruginosa, and B. fragilis. It mildly inhibits the growth of Gram-positive bacteria and dermatophytes with MIC values ranging from <6.25 to 25 μg mL. Intravenous administration of actinopyrone A (30 μg kg) increases coronary blood flow in dogs by 196.2%.

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).

P38α Inhibitor 2, a potent and selective inhibitor of p38α MAPK, exhibits a pIC50 value of 9.6. It also demonstrates inhibition of the hERG ion channel (IC50=27 μM) and maintains promising selectivity, with <30% inhibition across a panel of 51 protein kinases at a 10 μM concentration and a broad specificity against 141 other biological targets[1].

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd < 10 pM). The compound selectively binds to α4β1 (IC50 = 1.8 nM) over various other integrins and results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2].

Pestalotin is a fungal metabolite originally isolated from P. cryptomeriaecola with diverse biological activities. It induces reducing sugar release in embryoless rice endosperms when used at concentrations ranging from 3 to 100 mg L and enhances growth of rice seedlings (O. sativa) when used in combination with gibberellin A3 at concentrations ranging from 30 to 500 mg L. Pestalotin has antifungal activity, reducing the growth of C. albicans, C. neoformans, T. rubrum, and A. fumigatus (MICs = 12.5, 50, 50, and 50 μg ml, respectively). It is cytotoxic to HL-60, MKN45, LoVo, and A549 cells (IC50s = 64.87-182.92 μM). Pestalotin has been used as a standard for dereplication of natural products.

Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993). Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4 References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993).

Rec 15/2615 is an antagonist of α1B-adrenergic receptors (α1B-ARs; Ki = 0.45 nM for the recombinant human receptor).1 It selectively inhibits α1B-ARs over α1A-, α1D-, and α1L-ARs (Kis = 7.59, 10.23, and 49 nM, respectively). Rec 15/2615 inhibits norepinephrine-induced contractions of isolated rabbit prostate and urethral strips (Kis = 100 and 316.2 nM, respectively), as well as reduces norepinephrine-induced contractions of chloroethylclonidine-precontracted isolated rabbit aortic rings (Ki = 50 nM).2 It decreases diastolic blood pressure (ED25 = 183 μg/kg, i.v.) and increases intracavernous pressure in anesthetized dogs when administered intracavernously at doses ranging from 30 and 1,000 μg/kg.1,2 |1. Sironi, G., Colombo, D., Poggesi, E., et al. Effects of intracavernous administration of selective antagonists of α1-adrenoceptor subtypes on erection in anesthetized rats and dogs. J. Pharmacol. Exp. Ther. 292(3), 974-981 (2000).|2. Testa, R., Guarneri, L., Angelico, P., et al. Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): Role of the alpha-1L adrenoceptor in tissue selectivity, part II. J. Pharmacol. Exp. Ther. 281(3), 1284-1293 (1997).

VPC03090 is a Sphingosine-1-Phosphate Receptor Inhibitor. VPC03090 is an analog of FTY-720, acts as antagonist for S1PR1 and S1PR3. VPC03090-P, converted from VPC03090 through the phosphorylation by SK-2, causes a reduction in tumor growth in mice with mammary cancer, and its oral bioavailability is determined to be 30 hours.

ω-Agatoxin IVA TFA is a potent selective inhibitor of P Q type Ca2+ (Cav2.1) channels, with IC50 values of 2 nM for P-type and 90 nM for Q-type channels. It effectively inhibits glutamate exocytosis and calcium influx induced by high potassium, with IC50 values ranging from 30 to 225 nM. Additionally, it blocks high potassium-induced serotonin and norepinephrine release, without impacting L-type or N-type calcium channels [1][2].

Bovine Myeloid Antimicrobial Peptide (BMAP) 28, a synthetic peptide derived from bovine cathelicidin-5 (amino acids 132-158), exhibits antimicrobial activity against E. coli, S. aureus, MRSA, S. epidermidis, and the fungus C. albicans, with minimum inhibitory concentrations (MICs) of 2, 2, 4, 1, and 8 µM respectively. At a concentration of 200 nM, BMAP 28 permeabilizes the inner membrane of E. coli, and at 5 µM, it inhibits herpes simplex virus 1 (HSV-1) replication in Vero 76 cells. Furthermore, at 30 µM, it causes hemolysis in human erythrocytes and cytotoxicity in human neutrophils. In vivo, a dose of 0.8 mg/kg enhances survival in mice infected with E. coli or MRSA, but not P. aeruginosa.