SHP2 protein degrader-1 is a potent allosteric inhibitor of SHP2. SHP2 protein degrader-1 induces SHP2 degradation and cell apoptosis. SHP2 protein degrader-1 has the potential for researching SHP2 related diseases[1].
Phenyltoloxamine (Bistrimin) is an antihistamine agent with sedative and analgesic effects. Phenyltoloxamine also has potent Sigma-1 receptor binding affinity (Ki: 160 nM)[1][2][3].
Tyrosinase (206-214), human (AFLPWHRLF), a 9-amino acid peptide, is a tyrosinase epitope. Tyrosinase (206-214), human can be recognized by HLA-A24 restricted, tumor-infiltrating lymphocytes (TIL)[1].
Tebuconazole is an agricultural azole fungicide which can also inhibit CYP51 with IC50s of 0.9 and 1.3 μM for Candida albicans CYP51 (CaCYP51) and truncated Homo sapiens CYP51 (Δ60HsCYP51), respectively.
Neorauflavane is a potent tyrosinase inhibitor derived from Campylotropis hirtella, with an IC50 value of 30 nM for tyrosinase monophenolase activity and an IC50 value of 500 nM for diphenolase activity. Neorauflavane can effectively reduce the melanin content of B16 melanoma cells[1].
FXIa-IN-8 is a potent and selective FXIa inhibitor with an IC50 of 14.2 nM. FXIa-IN-8 shows antithrombotic activity without increasing the bleeding risk and obvious toxicitysup>[1].
NIM811 (SDZ NIM811) is a potent mitochondrial permeability transition inhibitor. Sequence: Cyclo[{Aaa}-{Abu}-{Sar}-Ile-Val-Leu-Ala-{D-Ala}-Leu-Leu-Val].
Calpain Inhibitor XI is a reversible covalent inhibitor of calpain-1. Calpain Inhibitor XI can be used for the research of neurodegenerative disorders[1].
SC-57461A is a potent, orally active, nonpeptide, and selective inhibitor of Leukotriene A4 (LTA4) hydrolase with IC50s of 2.5 nM, 3 nM, and 23 nM for recombinant human, mouse, and rat LTA4 hydrolase, respectively[1].
Cilazapril is a angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and congestive heart failure.Target: ACECilazapril is a new nonthiol group containing angiotensin converting enzyme (ACE) inhibitor. Cilazapril has been investigated in more than 4000 patients with all degrees of hypertension, as well as in the special patient groups such as the elderly, renally impaired, and patients with concomitant diseases, such as congestive cardiac failure or chronic obstructive pulmonary disease [1]. Cilazapril is a very potent and highly effective converting enzyme inhibitor. Doses well below 5 mg/day will probably suffice for therapeutic efficacy [2].
Thalidomide is initially promoted as a sedative, inhibits ereblon (CRBN), a part of the cullin-4 E3 ubiquitin ligase complex CUL4-RBX1-DDB1, with a Kd of ∼250 nM, and has immunomodulatory, anti-inflammatory and anti-angiogenic cancer properties.
HS-131, a near infrared dye tethered Hsp90 inhibitor, is able to detect oncogene-driven breast cancers, including multiple different molecular subtypes of human breast cancers[1].
HX600 is a synthetic agonist for RXR (Retinoid X Receptor) heterodimer complex. HX600 prevents ischemia-induced neuronal damage. HX600 has orally bioactivity[1].
CAY10594 is a potent phospholipase D2 (PLD2) inhibitor both in vitro (IC50=140 nM) and in cells (IC50=110 nM)[1]. CAY10594 strongly inhibits the invasive migration of breast cancer cells in vitro and ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis[2].
Sp-cAMPS triethylamine, a cAMP analog, is potent activator of cAMP-dependent PKA I and PKA II. Sp-cAMPS triethylamine is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a Ki of 47.6 µM. Sp-cAMPS triethylamine binds the PDE10 GAF domain with an EC50 of 40 μM[1][2][3].
Fluorobexarotene (compound 20) is a potent retinoid-X-receptor (RXR) agonist, with a Ki value of 12 nM and an EC50 value of 43 nM for RXRα receptor. Fluorobexarotene possesses an apparent RXR binding affinity that is 75% greater than Bexarotene[1].
7ß,27-Dihydroxycholesterol (7β, 27-OHC) is a potent and selective activator of RORγt (Ki=120 nM). 7ß,27-Dihydroxycholesterol promotes the differentiation of mouse and human CD4+ Th17 cells. 7ß,27-Dihydroxycholesterol also increases the production of IL-17 depended on CYP27A1[1].
Cbl-b-IN-12 (Example 10) is a casitas B-lineage lymphoma-b (CBL-B) inhibitor with an IC50 of <100 nM[1].
Entacapone is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM for PD treatment.IC50 Value: 151 nMTarget: COMTin vitro: Entacapone inhibits catechol-O-methyltransferase(COMT) with similar IC50 in different tissues including live, duodenum, kidney and lung, but entacapone is more active than tolcapone in those tissues. Entacapone (< 100 μM) is a potent inhibitor of α-syn and β-amyloid (Aβ) oligomerization and fibrillogenesis, and also protects against extracellular toxicity induced by the aggregation of both proteins in PC12 cells.in vivo: Levodopa/carbidopa/entacapone has been shown to improve the pharmacokinetic profile of levodopa and provide superior symptomatic control compared with conventional levodopa/dopa decarboxylase inhibitor therapy. We report four case histories describing clinical experience of using levodopa/carbidopa/entacapone 200/50/200 mg, one of the latest doses of this formulation, in a range of patients with Parkinson's disease. These cases illustrate that levodopa/carbidopa/entacapone 200/50/200 mg provides improvements in symptomatic control.Clinical trial: The combination product carbidopa/levodopa/entacapone (CLE) was approved in 2003 for the treatment of PD patients.
MK-2048 is a potent inhibitor of integrase and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively.IC50 Value: 2.6 nM for HIV IntegraseTarget: HIV IntegraseMK-2048 is a second generation integrase inhibitor, intended to be used against HIV infection. MK-2048 inhibits subtype B and subtype C integrase activities. MK-2048 inhibits R263K mutants slightly more effectively than G118R mutants. MK-2048 inhibits S217H intasome and, by contrast, MK-2048 remains fully active against the N224H intasome. MK-2048 displays substantially lower dissociation rates compared with raltegravir, another integrase inhibitor. MK-2048 is active against viruses resistant to RAL and EVG. MK-2048 exposure leads to the selection of G118R as a possible novel resistance mutation after 19 weeks. MK-2048, with continued pressure, subsequently leads to an additional substitution, at position E138K, after 29 weeks, within the IN gene. Although the G118R mutation alone confers only slight resistance to MK-2048 but not to RAL or EVG, its presence arouses a dramatic reduction in viral replication capacity compared to wild-type NL4-3. E138K both partially restores viral replication capacity and also contributes to increased levels of resistance against MK-2048.
AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively.
DB04760 (compound 4) is a potent, highly selective, non-zinc-chelating MMP-13 inhibitor with an IC50 of 8 nM[1]. DB04760 significantly reduces paclitaxel neurotoxicity and has anticancer activity[2].
ROCK2-IN-7 is a kinase inhibitor targeting to ROCK2. ROCK2-IN-7 inhibits ROCK2/pSTAT3 Signaling. ROCK2-IN-7 suppresses systemic immunity activation and attenuates inflammation in psoriasis model[1].
Valopicitabine (NM283) dihydrochloride is a nucleoside analog and the orally bioavailable prodrug of the potent anti-HCV agent 2'-C-methylcytidine (NM107). NM107competitively inhibits NS5B polymerase, causing chain termination[1][2].
(R)-Azasetron besylate (SENS-401) is an orally active calcineurin inhibitor. (R)-Azasetron besylate reduces Cisplatin (HY-17394)-induced hearing loss and cochlear damage[1][2].
FTI-277 Hcl is an inhibitor of farnesyl transferase (FTase); a highly potent Ras CAAX peptidomimetic which antagonizes both H- and K-Ras oncogenic signaling.IC50 value:Target: FTase inhibitorin vitro: Treatment with FTI-277 (20 microM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radiosensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G(2)/M-phase arrest in both cell types [1]. Treatment of PC-3 cells with GGTI-298 and FTI-277 inhibited migration and invasion in a time- and dose-dependent manner [3].in vivo: FTI-277 treatment prevented increased PTP-1B and PTEN protein expression in burned mice as compared with vehicle alone. In contrast, FTI-277 did not significantly alter protein expression of PTP-1B and PTEN in sham-burned mice [2].
Dorzolamide Hcl(L671152 Hcl; MK507 Hcl) is an anti-glaucoma agent, which is a carbonic anhydrase inhibitor.Target: carbonic anhydrase (CA)Dorzolamide hydrochloride is a carbonic anhydrase inhibitor. It is an anti-glaucoma agent, and acts by decreasing the production of aqueous humour [1]. Glaucoma was induced in the right eye of adult Wistar rats by episcleral venous occlusion. One experimental group was administered dorzolamide hydrochloride 2%-timolol 0.5% combination eye drops, while the other experimental group was administered dorzolamide hydrochloride2% eye drops. Control groups had surgery without drug administration. Drug application was initiated either 2 weeks before surgery (Group A), from the day of surgery (Group B), 2 weeks after surgery (Group C), or 4 weeks after surgery (Group D). RGCs were labeled by intratectal Fluorogold injections and counted from flat-mount preparations, and IOP was measured using Tonopen. Both dorzolamide-timolol combination and dorzolamide hydrochloride, when applied topically, significantly reduced IOP and improved RGC densities in experimental eyes when compared to control eyes. Earlier initiation, as well as longer duration of drug application, resulted in higher RGC densities [2].Clinical indications: Glaucoma; Ocular hypertensionFDA Approved Date: 1995Toxicity: Dizziness, headache, shortness of breath, slow heartbeat, severe asthma, cardiac arrest
CM-675 is a dual phosphodiesterase 5 (PDE5) and class I histone deacetylases-selective inhibitor, with IC50 values of 114 nM and 673 nM for PDE5 and HDAC1, respectively. CM-675 has potential to treat Alzheimer’s disease[1].
RORγ-IN-1 is a RORγ inhibitor extracted from patent US 9481674 B1, has a Ki of <100 nM.
Bivalirudin Trifluoroacetate is a synthetic 20 residue peptide which reversibly inhibits thrombin.IC50 Value:Target: thrombinin vitro: Eptifibatide (8 mg/mL) added together with a low (70 ng/mL) concentration of bivalirudin (a direct thrombin inhibitor) effectively (approximately 90%) reduced platelet aggregation induced by thrombin (0.2 U/mL) [1]. In thrombin generation assay (TGA), bivalirudin had no effect on these parameters up to 10 μmol/l [2]. Bivalirudin-facilitated binding of MPO to BAEC resulted also in functional changes in terms of increased NO consumption as well as enhanced MPO-mediated redox modifications [3].in vivo: The use of bivalirudinprevented further increase in antiheparin/PF4 antibody IgG levels in rats [4]. Three animals in the 500-mg/kg/24 h group, and 7 animals in the 2000-mg/kg/24 h group in the toxicokinetic assessment phase of the study were found dead or euthanized in extremis (following blood sampling). Plasma concentrations of bivalirudin appeared to be linear and dose independent [5].Clinical trial: Antithrombotic Effects of Ticagrelor Versus Clopidogrel . Phase 4