minimal

DORA-22 is a dual orexin receptor antagonist, improves mild stress-induced insomnia with minimal effect on memory

TMC647055 Choline Hydroxide Salt is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase which potentially for the treatment of HCV infection. It has nanomolar cellular potency (EC(50) of 82 nM) with minimal associated cell toxicity (CC(

AMARA peptide acetate is a substrate for SIK and AMPK.AMARA peptide is a minimal substrate of several members of the protein kinases family. It consists of the phosphorylation site for AMP-activated Protein Kinase (AMPK).

TCMDC-135051 is a potent and selective PfCLK3 protein kinase inhibitor demonstrating significant antiparasiticidal activity (EC50=320 nM) while exhibiting minimal off-target toxicity. It effectively hinders the transition from trophozoite to schizont, impairs transcription, and diminishes transmission to the mosquito vector.

INU-152 is a pan-RAF inhibitor. INU-152 has potent anti-tumor activity in preclinical models of BRAFV600E mutant cancer. INU-152 inhibits all RAF isoforms and inhibits MAPK pathways in mutant BRAF cells. INU-152 exhibits minimal paradoxical pathway activa

Vesnarinone (Arkin) (INN) is a mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. It also suppresses cell proliferation and induces apoptosis by inducing the expression of p21, an inhibitor of cyclin-dependent kinase activity in p53-mediated cell cycle arrest.

PF-06459988 is a novel, effective, orally active, irreversible, and selective epidermal growth factor receptor (EGFR) mutant inhibitor. PF-06459988 has high efficiency and high affinity for EGFRs double mutants containing T790M, and has minimal activity against WT EGFR. PF-06459988 makes a candidate drug for the treatment of cancer.

Citalopram hydrobromide (XU-62-320) , a selective serotonin reuptake inhibitor (SSRI), selectively inhibits the CNS neuronal reuptake of serotonin, thereby potentiating serotonergic activity in the central nervous system (CNS). Citalopram hydrobromide is the orally bioavailable hydrobromide salt of the racemic bicyclic phthalene derivative citalopram with antidepressant activity. This agent has minimal effects on the CNS neuronal reuptake of norepinephrine (NE) and dopamine (DA).

Fidaxomicin (Tiacumicin B) is a semisynthetic macrolide antibiotic used to treat Clostridium difficile-associated diarrhea in adults. Fidaxomicin has minimal systemic absorption and has not been linked to serum enzyme elevations during therapy or to instances of clinically apparent, acute liver injury.

Pitavastatin calcium (NK-104) is a potent inhibitor of HMG-CoA reductase (Ki: 1.7 nM). It lowers both total cholesterol and low-density lipoprotein cholesterol in animals and humans. Metabolism of pitavastatin by the cytochrome P450 system is minimal, reducing the risk of drug-drug interactions.

ONX-0914 (PR-957) is an effective and specific immunoproteasome inhibitor, which has minimal cross-reactivity for the constitutive proteasome.

Phenylacetyl-coenzyme A (CoA) is a key intermediate in aerobic catabolism of phenylacetate in bacteria such asPseudomonas, when cultured in minimal media using phenylacetate as the sole carbon source.1It is a precursor in the synthesis of the antibiotic penicillin G found in industrial strains ofP. chrysogenum. Phenylacetyl-CoA also acts as an effector molecule of the TetR family transcriptional repressor PaaR inT. thermophilusand the GntR family transcriptional regulator PaaX inE. coliandPseudomonas, binding to each protein to induce derepression of various genes.2

WL47 is a high-affinity ligand for caveolin-1 (CAV1) with a dissociation constant (Kd) of 23 nM, demonstrating potent disruption of CAV1 oligomers. This compound exhibits selectivity for CAV1, with minimal interaction towards BSA, casein, and HEWL. Notably, WL47's molecular structure is 80% smaller than its T20 parent sequence, rendering it a useful tool for investigating caveolin-1 function [1].

WAY-639872 is an active molecule exhibiting (in vivo) efficacy. This compound selectively targets (enzyme X), demonstrating inhibition with an IC50 of 2 nM. Importantly, it possesses a (high level) of specificity, showing minimal interaction with related enzymes. WAY-639872 maintains stability (under physiological pH), and its pharmacokinetic profile indicates an (excellent oral bioavailability) of 90%. Furthermore, the molecule remains unmetabolized for an extended period, with a half-life exceeding 24 hours. Its safety profile reveals no significant (adverse effects), and it has successfully completed Phase I clinical trials.

Compound 11, also known as Antitumor Photosensitizer-2, is a potent photosensitizer with remarkable photodynamic anti-tumor properties and minimal skin photo-toxicity, representing a promising candidate for photodynamic therapy research [1].

Lancifodilactone F exerts minimal cytotoxicity against C8166 cells (CC50 > 200 microg/mL) and shows anti-HIV activity with EC50 = 20.69 +/- 3.31 microg/mL and a selectivity index > 6.62.

R-(+)-Cotinine ((+)-Cotinine), a metabolite of Nicotine, demonstrates minimal activity across numerous pharmacological targets. However, it is capable of enhancing the acetylcholine (Ach)-evoked current in human α7 nicotinic acetylcholine receptors (nAChRs) [1].

Tarlatamab (AMG-757) is a first-in-class, high-affinity, bispecific T-cell engager (BiTE) antibody that selectively targets delta-like ligand 3 (DLL3), a protein predominantly expressed in small-cell lung cancer (SCLC) tumors with minimal expression in normal tissues. It demonstrates dissociation constants (KDs) of 0.64 nM and 0.50 nM for DLL3 in human and nonhuman primates (NHP), respectively, and 14.9 nM and 12 nM for CD3 in human and NHP, accordingly. As a pioneering HLE BiTE immuno-oncology therapy for DLL3-expression SCLC, tarlatamab shows promising potential for research in this area [1].

Mollicellin I (compound 1), a depsidone, exhibits minimal growth inhibitory activity against human breast cancer (Bre04), human lung (Lu04), and human neuroma (N04) cell lines, with GI50 values exceeding 10 μg/mL [1].

Antitumor agent-67 (compound 3), a potent antitumor agent, exhibits highly selective toxicity toward cancer cells while sparing normal cells. This compound can be activated by NQO1 to effectively release podophyllotoxin, thereby killing tumor cells. In HepG2 xenograft models, Antitumor agent-67 significantly inhibits cancer growth with minimal toxicity [1].

Pierreione B is an inhibitor of mTOR signaling with strong anticancer activity. Pierreione A and Pierreione B demonstrate solid tumor selectivity with minimal cytotoxicity.

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

Peptide 5f, sourced from wasp venom, exhibits antimicrobial properties effective against both bacterial and fungal pathogens, while demonstrating minimal hemolytic activity on human red blood cells [1].

K1833 is an inhibitor and reactivator of human acetylcholinesterase (hrAChE), exhibiting an inhibition concentration (IC50) of 58$. Additionally, K1833 demonstrates potent inhibition (IC50 = 0.57$) and minimal reactivation of human butyrylcholinesterase (hrBChE) [1].

Gageotetrin C, an antimicrobial peptide sourced from the marine bacterium Bacillus subtilis, exhibits significant antifungal activity with a minimal inhibitory concentration (MIC) value of 0.02-0.04 μM [1].

MOG (35-55), human, a constituent of central nervous system myelin, is distinguishable from mMOG (35-55) due to a proline-to-serine substitution at position 42. It possesses immunogenic properties and is partially cross-reactive with mMOG35–55. However, MOG (35-55), human does not induce encephalitogenic effects, and only elicits minimal clinical signs of EAE (experimental autoimmune encephalomyelitis) in comparison to the rodent peptide.

GGTI298, a CAAZ peptidomimetic and potent geranylgeranyltransferase I (GGTase I) inhibitor, efficiently blocks the processing of geranylgeranylated Rap1A while exerting minimal impact on the processing of farnesylated Ha-Ras. The inhibitor displays in vivo IC50 values of 3 μM for Rap1A and >20 μM for Ha-Ras, respectively.

Homo-PROTAC cereblon degrader 1 is a highly potent and efficient cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3.

Pulrodemstat (CC-90011) is a highly potent and selective inhibitor of lysine specific demethylase-1 (LSD1). It exhibits a reversible mode of action and can be administered orally. With an impressive IC50 of 0.25 nM, Pulrodemstat effectively suppresses the enzymatic activity of LSD1. Notably, it demonstrates minimal inhibition against LSD2, MOA-A, and MAO-B enzymes. Moreover, Pulrodemstat possesses remarkable anticancer properties, promoting differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells.

Lipid 5 is an amino lipid compound that demonstrates proficient mRNA delivery in rodent and primate models, displaying favorable pharmacokinetics and minimal toxicity.

METTL3-IN-5 (Compound 13) serves as an inhibitor of METTL3 and demonstrates efficacy in suppressing MOLM-13 cell growth with an IC50 of less than 2 μM. Moreover, it exhibits minimal hERG inhibitory activity, with an IC50 greater than 30 μM, rendering it suitable for AML research [1].

Antitumor Photosensitizer-1 (Compound 8) is a potent photosensitizer with remarkable photodynamic anti-tumor properties and minimal skin photo-toxicity, positioning it as a promising new candidate for photodynamic therapy research [1].

Antiparasitic Agent-19 (Compound 40) is a broad-spectrum antiparasitic with minimal toxicity to Trypanosoma brucei, Leishmania infantum, and Trypanosoma cruzi [1].

Justicidin C, a lignan compound, exhibits potent antiviral properties, particularly against vesicular stomatitis virus, with minimal cytotoxicity observed in rabbit lung cells (RL-33) [1].

Neocyclomorusin displays minimal inhibitory concentration (MIC) value of 4 ug/mL against Klebsiella pneumoniae ATCC11296, Enterobacter cloacae BM47.

AMARA peptide is a substrate for SIK and AMPK.AMARA peptide is a minimal substrate of several members of the protein kinases family. It consists of the phosphorylation site for AMP-activated Protein Kinase (AMPK).

C14-4, an ionizable lipid utilized in lipid nanoparticles (LNPs) formulation, has been recognized for its efficacy in transfection and minimal cytotoxicity.

Efrotomycin, an orally active antibiotic derived from Streptomyces lactamdurans, exhibits minimal impact on the quantity, duration, shedding rate, and antimicrobial susceptibility of Salmonella typhimurium in infected pigs [1] [2].

mTOR Inhibitor-14 (compound 14c) is a potent inhibitor of mTOR with minimal inhibition of CYP2C8 and has demonstrated the capability to inhibit tumor growth [1].

Antitumor agent-29 is a hepatocyte-targeting prodrug with demonstrated efficacy and minimal toxicity in anticancer applications.

Moenomycin complex is a mixture of moenomycins A, A12, C1, C3 and C4, which are antibiotics isolated from several strains of Streptomyces that directly inhibit bacterial peptidoglycan glycosyltransferases. [1] The minimal inhibitory concentration of moenomycin A against various Gram-positive bacteria ranges from 1-100 nM.[1]

OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosis H37Rv (MIC: 0.0005 μg/ml) and Kurono (MIC: 0.0005 μg/ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg/ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg/ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg/ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg/kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1/2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg/kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg/kg to 2.5 mg/kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg/kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.

Endotoxin Inhibitor TFA is a synthetic peptide that exhibits high-affinity binding to lipid A, effectively detoxifying LPS and impeding LPS-induced cytokine release in vivo. It also suppresses the febrile response to LPS while demonstrating minimal toxicity and lethality [1].

ER degrader 6 (compound 35s) is a potent selective estrogen receptor modulator (SERM) with the capacity to degrade Estrogen Receptor (ER)α. It disrupts the microtubule network, inhibiting tubulin polymerization, and effectively suppresses tumor growth with minimal toxicity [1].

SARS-CoV-2 3CLpro-IN-14 (compound 11j) is an orally active inhibitor of SARS-CoV-2 3CLpro, demonstrating potent anti-SARS-CoV-2 properties with an EC50 of 0.18 μM and exhibits minimal cytotoxicity, having a CC50 greater than 50 μM, in Vero E6 cells [1].

Pentadecanoyl ethanolamide, a derivative of the endogenous lipid amides (N-acylethanolamines), demonstrates anticonvulsant efficacy in electroshock-induced seizures in mice, exhibiting minimal toxicity [1].

PD-L1-IN-1, a powerful PD-L1 inhibitor, demonstrated an IC50 of 115 nM. By forming a robust bond with the PD-L1 protein, PD-L1-IN-1 effectively suppressed tumor growth by enhancing the antitumor immune activity of peripheral blood mononuclear cells in co-cultures with PD-L1 expressing cancer cells (PC9 and HCC827 cells). It significantly elevated the release of interferon γ and induced apoptosis in cancer cells, while exhibiting minimal cytotoxicity in healthy cells [1].

PD-321852 is a small-molecule Chk1 inhibitor, which potentiates gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD-321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines.

Cap-dependent endonuclease-IN-9 is a potent (CEN) inhibitor with notable efficacy against the influenza virus and exhibits minimal cytotoxicity, enhanced in vivo pharmacokinetics, and robust pharmacodynamics. It effectively suppresses the RNA polymerase activity of A virus[1].

PD-1/PD-L1-IN-27 is a potent inhibitor of PD-1/PD-L1, exhibiting an IC50 of 134 nM and demonstrating antitumor effects with minimal T cell cytotoxicity. It activates CD8+ T cells and mitigates T cell exhaustion [1].

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Zonisamide sodium is a 1,2 benzisoxazole derivative. It is the first agent of this chemical class to be developed as an antiepileptic drug.