Cytochrome P450 Inhibitor

Exemestane-d₂ is the deuterium labeled Exemestane. Exemestane (FCE 24304) is a selective, irreversible and orally active steroidal aromatase inhibitor with IC₅₀s of 30 nM and 40 nM for human placental and rat ovarian aromatase, respectively. Exemestane can be used for hormone-dependent breast cancer research.

Flavanone (Standard) is the analytical standard of Flavanone. This product is intended for research and analytical applications. Flavanone is a naturally occurring flavone. Flavanone has inhibitory activity for human estrogen synthetase (aromatase). lavanone is the inhibitor for ERK/p38/NF-κB signaling pathway. Flavanone exhibits oral activity and antitumor efficacy.

RET-IN-31 (Compound 13) is an orally active, selective RET inhibitor (IC₅₀s: 1.4 nM, 1.9 nM, 3.8 nM for RET^WT, RET^V804L, RET^V804M, respectively). RET-IN-31 inhibits hERG and Cytochrome P450 (IC₅₀s: 13.6 μM, 7.9 μM, 12.8 μM, 16.9 μM, 8.9 μM, 13.0 μM for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4-M, CYP3A4-T, respectively). RET-IN-31 has anti-cancer effects against activated RET mutations and gene fusion-driven cancers.

Stiripentol-d₉ is the deuterium labeled Stiripentol. Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with K_is of 1.59±0.07 and 0.516±0.065 μM and IC₅₀ of 1.58 and 3.29 μM, respectively.

CYP51/PD-L1-IN-3 (compound L21) is a quinazoline compound with antifungal activity. CYP51/PD-L1-IN-3 is a dual inhibitor of CYP51 (IC₅₀: 0.205 μM) and PD-L1 (IC₅₀: 0.039 μM), which can induce early apoptosis of fungal cells in the cell cycle. CYP51/PD-L1-IN-3 also significantly reduced intracellular IL-2, NLRP3, and NF-κBp65 protein levels, induced mitochondrial damage and ROS accumulation, and ultimately led to fungal lysis and death.

Cholesterol 24-hydroxylase-IN-3 is an orally active, selective, and blood-brain barrier-penetrant CH24H inhibitor (IC₅₀ = 23 nM) belonging to 1,3-oxazole derivatives. Cholesterol 24-hydroxylase-IN-3 competitively inhibits CH24H enzyme activity by using the 1,3-oxazole nitrogen atom to coordinate the heme iron and the cyclopropyl group occupying the hydrophobic pocket. Cholesterol 24-hydroxylase-IN-3 can be used for research on epilepsy and other neurological diseases.

KBP-7018 hydrochloride is an orally active, tyrosine kinase-selective multi-kinase inhibitor with an IC₅₀ value of 10 nM against c-KIT, 7.6 nM against RET, and 25 nM against human PDGFR. KBP-7018 hydrochloride improves survival rates in a mouse model of pulmonary fibrosis. KBP-7018 hydrochloride can be used in research related to idiopathic pulmonary fibrosis.

Proadifen (hydrochloride) (Standard) is the analytical standard of Proadifen (hydrochloride). This product is intended for research and analytical applications. Proadifen (SKF-525A) hydrochloride is a non-competitive Cytochrome P450 inhibitor with an IC50 value of 19 μM. Proadifen hydrochloride reduces monoamine oxidase A (MAO-A) activity and reverses the antidepressantlike behavioral effect of Imipramine (HY-B1490A) and Desipramine (HY-B1272A) in rats. Proadifen hydrochloride also reduces N, N-dimethyltryptamine (DMT) metabolism in liver microsomes and inhibits N-demethylationand Acridone (HY-W007771) formation. Proadifen hydrochloride augments Lipopolysaccharide (LPS) (HY-D1056)-induced fever and exacerbates Prostaglandin E2 (PGE2) (HY-101952) levels in the rat. Proadifen hydrochloride is promising for research of metabolism-related deseases, ovarian carcinoma, inflammation and dopamine neurons-related deseases[4].

Debutyldronedarone hydrochloride (Standard) (SR35021 hydrochloride (Standard)) is the analytical standard of Debutyldronedarone (hydrochloride) (HY-12753A). This product is intended for research and analytical applications. Debutyldronedarone hydrochloride (SR35021 hydrochloride) is a Cytochrome P450 enzyme inhibitor and a Thyroid Hormone Receptor inhibitor, and it is a metabolite of Dronedarone (HY-A0016). Debutyldronedarone hydrochloride inhibits the binding of T3 to TRα1 and TRβ1. Debutyldronedarone hydrochloride reduces the incidence of reperfusion-induced ventricular fibrillation in anesthetized rats, while decreasing their heart rate and blood pressure. Debutyldronedarone hydrochloride can be used in studies related to ventricular fibrillation and atrial fibrillation.

3,4-Methylenedioxyphenmetrazine (3,4-MDPM) hydrochloride is a psychoactive substance. 3,4-Methylenedioxyphenmetrazine exhibits strong CYP2D6 inhibition and moderate inhibition of CYP3A4 and CYP1A2.

5,7,2',6'-Tetrahydroxyflavone is a natural flavonoid that inhibits hepatic testosterone 6β-hydroxylation (CYP3A4) activity with an IC₅₀ of 7.8 μM.

EGFR/DHFR-IN-2 (9b) is a dual h-DHFR/EGFR^TK inhibitor, with IC₅₀ values of 0.192 μM and 0.109 μM for h-DHFR and EGFR, respectively. EGFR/DHFR-IN-2 (9b) halts the cell cycle at the G1/S phase and induces apoptosis. EGFR/DHFR-IN-2 (9b) is a potential inhibitor of CYP2C9 and CYP3A4. EGFR/DHFR-IN-2 (9b) can be used in the cancer research.

CD564 (Compound 11b) is a cytochrome P450 CYP26A1 and CYP26B1 inhibitor, with IC₅₀ values of 1.63 μM and 0.52 μM, respectively. Cytochrome P450 CYP26 enzymes clear all-trans retinoic acid (atRA).

CYP51-IN-16 (compound C6) is a phenylpyrimidine CYP51 inhibitor, and shows antifungal activity in in vitro. CYP51-IN-16 inhibits tumor cell growth.

CYP51-IN-21 (Compound A33) is a potent CYP51 inhibitor. CYP51-IN-21 shows excellent antifungal activities against pathogenic fungi and drug-resistant strains. CYP51-IN-21 inhibits the formation of fungal biofilm.

Benoxaprofen-¹³C, d₃ is the ¹³C-labeled Benoxaprofen (HY-13568). Benoxaprofen (LRCL 3794) is a nonsteroidal anti-inflammatory agent that blocks the biosynthesis of inflammatory mediators such as leukotrienes and prostaglandins by inhibiting 5-LOX, PGH2 synthase and cytochrome P-450. Benoxaprofen exhibits significant toxicity: it not only alters cellular redox status, uncouples oxidative phosphorylation and disrupts calcium ion homeostasis, but also causes liver injury through the formation of covalent adducts between its active metabolites and hepatic proteins. Benoxaprofen shows strong phototoxicity under ultraviolet irradiation, and induces erythrocyte lysis, mast cell degranulation and histamine release. Benoxaprofen is widely used in studies of urticaria and related phototoxic mechanisms.

(±)-ε-Viniferin is a racemate of ε-Viniferin (HY-N3841). (±)-ε-Viniferin exhibits P450 inhibitory antioxidants, as well as hepato-protective and antimicrobial activities. (±)-ε-Viniferin has antibacterial and antibiofilm activity against Gram-positive bacteria Streptococcus pneumoniae with a MIC of 20 μM.

Antifungal agent 175 is a potent antifungal agent with an EC₅₀ of 1.8 μg/mL against R. solani. Antifungal agent 175 Z17 exerts its effects primarily by disrupting the cell membranes of pathogenic fungi to trigger lipid peroxidation and oxidative stress, inhibiting pyruvate kinase (PK) to interfere with energy metabolism, and binding to the cytochrome bc1 complex. Antifungal agent 175 can be used in research on rice sheath blight.

Gestodene-d₆ (SHB 331-d₆; WL 70-d₆) is the deuterated-labeled Gestodene (HY-B0110). Gestodene is an orally active synthetic progestogen compound of the 19-nortestosterone class. Gestodene binds with high affinity to the progesterone receptor, inhibits 5α-reductase, binds to androgen and aldosterone receptors, and inactivates CYP3A. Gestodene acts as a positive allosteric modulator of PAR1, enhances PAR1-mediated signaling pathways, and is capable of increasing the activation potency of PAR1-AP toward PAR1, thereby promoting ERK1/2 phosphorylation, receptor internalization, cell morphological changes, and human platelet aggregation. Gestodene and its A-ring reduced metabolites promote the proliferation, differentiation, and mineralization of neonatal rat osteoblasts. Gestodene itself has no binding capacity for estrogen receptors, and this osteogenic activity depends on intracellular metabolism to generate A-ring reduced products with estrogen-like agonistic activity. Gestodene is useful for research on diseases related to progesterone secretion and diseases related to thrombosis.

Polθ-IN-10 is an orally active Polθ-pol inhibitor (with a human IC₅₀ of 1.3 nM) that exhibits oral bioavailability in mice and rats. Polθ-IN-10 binds to the allosteric site of Polθ-pol, disrupts the microhomology-mediated end-joining DNA repair pathway, and inhibits CYP2C9 (IC₅₀=1.63 μM). Polθ-IN-10 selectively inhibits the proliferation of HR-deficient cancer cells and induces apoptosis. Polθ-IN-10 is applicable to the research of HR-deficient cancers.