Ionizable Lipid Products

Ezutromid is a novel Small utrophin's translation modulator with EC50 of 0.4 uM .In vitro: 1) SMT C1100 induces increased levels of utrophin RNA in human muscle cells.2) Treatment of human DMD cells with SMT C1100 lead to a 2-fold increase in utrophin protein levels at an optimal concentration of 0.3 uM after 3 days of treatment. 3) SMT C1100 wassafe and well tolerated with plasma concentrations achieved suf?cient to cause a 50% increase in concentrations of utrophin in cells. 4) SMT C1100 led to a 30% increase in Utrn mRNA level and resulted in a 2.0-fold increase in UTRN protein level .In vivo: 1)The reference for administration is 50 mg/kg. 2) it was considered that no toxicity was determined for SMT C1100 administered by oral gavage to the mouse up to dose levels of 2000 mg/kg/day for 28 days.Note: You can dissolve the products in phosphate buffered saline (PBS), 0.1% Tween-20, 5% DMSO)

Letermovir is a novel inhibitor of CMV, which targets the viral terminase complex and remains active against virus resistant to DNA polymerase inhibitors.

E7046 is an orally bioavailable and specific EP4 antagonist, with IC50 of 13.5 nM and Ki of 23.14 nM, exhibiting anti-tumor activities.

Wnt-C59 (C59) is a highly potent and oral porcupine (PORCN) inhibitor with an IC50 of 74 pM.

BLU-554 is a potent fibroblast growth factor receptor 4 (FGFR4) inhibitor.

CC-115 is a potent and dual DNA-PK and mTOR kinase inhibitor with IC50s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.

CYM5442 is a potent, highly-selective and orally active sphingosine 1-phosphate (S1P1) receptor agonist with an EC50 of 1.35 nM. CYM5442 is inactive against S1P2, S1P3, S1P4, and S1P5. CYM5442 activates S1P1-dependent p42/p44-MAPK phosphorylation. CYM5442 exerts retinal neuroprotection. CYM5442 can easily penetrate the central nervous system (CNS)[1][2].

CMX001 (Brincidofovir; HDP-CDV) was developed as an orally active, lipophilic form of cidofovir (CDV); has enhanced activity in vitro and in vivo compared to CDV against certain herpesviruses, adenoviruses and orthopoxviruses.IC50 Value: 5.5 nM (EC50, in PDA at 7 dpi) [3]Target: anti-CMVCMX001 is currently in Phase II clinical studies for development as a therapeutic agent for human CMV, adenovirus and BK virus infections, as well as, for adverse events following smallpox vaccinations.in vitro: In PDA at 7 dpi, the CMX001 50% effective concentration (EC50) was 5.55 nM, the 50% cytotoxic concentration (CC50) was 184.6 nM, and the 50% selectivity index (SI50) was 33.3. The EC90 was 19.7 nM, the CC90 was 5,054 nM, and the SI90 was 256.1. In COS-7 cells, JCV replication was faster and the EC50 and EC90 were 18- and 37-fold higher than those in PDA, i.e., 0.1 μM and 0.74 μM (CC50, 0.67 μM; SI50, 6.7; CC90, 12.2 μM; SI90, 16.5) at 5 dpi [3].in vivo: CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra-nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other-day for 14 days provided solid protection against mortality and weight loss following an intra-nasal challenge of (100-200) x LD(50) of ectromelia virus [1]. When CMX001 was administered orally to mice infected with HSV-1, mortality was reduced significantly (p≤0.001) with all three dose levels when treatments were initiated 24 h post viral inoculation. When treatments were started 48 h post viral inoculation, 5 and 2.5 mg/kg significantly reduced mortality (p≤ 0.001). If treatments were delayed until 72 h post viral inoculation, CMX001 did not reduce mortality or increase the mean day to death. When mice were infected intranasally with HSV-1 and treatments initiated 24 h post viral inoculation using CMX001 at 5 mg/kg or ACV at 100 mg/kg, virus replication in target organs was reduced by both CMX001 and ACV when compared to vehicle treated mice [2]. Toxicity: Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose-limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed [4].

Varenicline(CP 526555;Champix) is a selective α4β2 nicotinic receptor partial agonist; it stimulates nicotine receptors more weakly than nicotine itself does.Varenicline(CP 526555; Champix; Chantix) is a prescription medication used to treat smoking addiction. As a partial agonist it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. Through these mechanisms Varenicline(CP 526555; Champix; Chantix) can assist some patients to quit smoking.

Mocetinostat (MGCD0103) is a potent, orally active and isotype-selective HDAC (Class I/IV) inhibitor with IC50s of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively. Mocetinostat shows no inhibition on HDAC4, HDAC5, HDAC6, HDAC7, or HDAC8.

CB-5083 is a novel first in class, potent orally bio-available p97 inhibitor that disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models . CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. CB-5083 showed activity to inhibit tumor growth in multiple rodent models of human cancer. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer.

Ivosidenib (AG-120) is a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor with an IC50 of 12 nM for mouse IDH1R132H.

Apabetalone (RVX-208) is an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. The IC50s are 87±10 μM and 0.51±0.041 μM for BD1 and BD2, respectively.

Etrasimod (APD334) is a potent, selective and orally available antagonist of the sphingosine-1-phosphate-1 (S1P1) receptor with an IC50 value of 1.88 nM in CHO cells.

(Z)-SU5614 is a potent FLT3 inhibitor and selectively induces growth arrest, apoptosis, and cell cycle arrest in Ba/F3 and AML cell lines expressing a constitutively activated FLT3[1].

LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies.

Bictegravir is a novel, potent inhibitor of HIV-1 integrase with an IC50 of 7.5 nM.

Toyocamycin (Vengicide) is an adenosine analog produced by Actinomycete, acts as an XBP1 inhibitor, inhibits IRE1α-induced ATP-dependent XBP1 mRNA cleavage, with an IC50 of 80 nM. Toyocamycin (Vengicide) induces apoptosis. Toyocamycin (Vengicide) shows no effect on IRE1α auto-phosphorylation[1].

ML364 is an inhibitor of ubiquitin specific peptidase 2 (USP2), and can be used for the research of breast cancer, extracted from patent WO 2016134026 A1, compound Figure 10G.

SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC50s of 34.3 nM for both GSK-3α and GSK-3β.