Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism.

Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.

Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.

References:
[1] Turk B, et al. EMBO J. 2012 Apr 4;31(7):1630-43.
[2] Eatemadi A, et al. Biomed Pharmacother. 2017 Feb;86:221-231.


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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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EC 144

EC144 is a potent and selective inhibitor of heat shock protein 90 (Hsp90) with an IC50 of 1.1 nM. EC144 inhibits tumor growth and causes partial tumor regressions. EC144 has the potential for the research of cancer diseases[1].

  • CAS Number: 911397-80-3
  • MF: C21H24ClN5O2
  • MW: 413.90100
  • Catalog: HSP
  • Density: 1.29±0.1 g/cm3(20 °C , 760mmHg)
  • Boiling Point: 674.1±65.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

CAXII-IN-1

CAXII-IN-1 (Compound 17) is a selective CA XII inhibitor with Ki values of 3.8 nM and 56.0 nM against hCA XII and hCA IX, respectively. CAXII-IN-1 shows antitumor activity[1].

  • CAS Number: 2479918-59-5
  • MF: C13H7Cl2NO3S
  • MW: 328.17
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Milvexian

Milvexian (BMS-986177), an effective antithrombotic agent, is an orally-bioavailable, reversible and direct inhibitor of human and rabbit factor XIa (FXIa) with Ki of 0.11, and 0.38 nM, respectively[1].

  • CAS Number: 1802425-99-5
  • MF: C28H23Cl2F2N9O2
  • MW: 626.44
  • Catalog: Factor Xa
  • Density: 1.60±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Arenarioside

Forsythoside F (Arenarioside) is a xanthine oxidase inhibitor and possesses antihyperuricemic effects in vivo[1].

  • CAS Number: 94130-58-2
  • MF: C34H44O19
  • MW: 756.70200
  • Catalog: Xanthine Oxidase
  • Density: 1.65 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLT3-IN-17

FLT3-IN-17 inhibits CYPs and FLT3 mutants activity (IC50s: <0.5 nM for D835Y). FLT3-IN-17 is also a FAK inhibitor, with an IC50 value of 12 nM. FLT3 ligand-2 can be used in the research of cancers[1].

  • CAS Number: 2758999-62-9
  • MF: C23H24N6O2S2
  • MW: 480.61
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WWL 70

WWL70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC50 of 70 nM.

  • CAS Number: 947669-91-2
  • MF: C27H23N3O3
  • MW: 437.490
  • Catalog: MAGL
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 653.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 348.8±31.5 °C

Elbasvir

Elbasvir (MK-8742) is a hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitor with EC50s of 4, 3 and 3 nM against genotype 1a, 1b, and 2a, respectively.

  • CAS Number: 1370468-36-2
  • MF: C49H55N9O7
  • MW: 882.017
  • Catalog: HCV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Hydroxybenzaldehyde

3-Hydroxybenzaldehyde is a precursor compound for phenolic compounds, such as Protocatechualdehyde (HY-N0295). 3-Hydroxybenzaldehyde is a substrate of aldehyde dehydrogenase (ALDH) in rats and humans (ALDH2). 3-Hydroxybenzaldehyde has vasculoprotective effects in vitro and in vivo[1].

  • CAS Number: 100-83-4
  • MF: C7H6O2
  • MW: 122.121
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 240.9±13.0 °C at 760 mmHg
  • Melting Point: 100-103 °C(lit.)
  • Flash Point: 98.6±12.4 °C

Deltasonamide 2

Deltasonamide 2 is a PDEδ inhibitor with a Kd of ~385 pM[1].

  • CAS Number: 2088485-34-9
  • MF: C30H39ClN6O4S2
  • MW: 647.25
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-9-IN-5

MMP-9-IN-5 is a MMP-9 inhibitor (IC50: 4.49 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-5 also inhibits AKT activity (IC50: 1.34 nM). MMP-9-IN-5 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-5 can be used in the research of cancers[1].

  • CAS Number: 2581824-80-6
  • MF: C27H20IN3O4
  • MW: 577.37
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-Glu-Glu-Val-Val-Ala-Cys-pNA

Ac-EEVVAC-pNA is a chromogenic substrate for a continuous spectrophotometric assay of HCV NS3 protease. The sequence EEVVAC is derived from the 5A-5B cleavage junction of the HCV polyprotein[1].

  • CAS Number: 389868-12-6
  • MF: C34H50N8O13S
  • MW: 810.872
  • Catalog: HCV Protease
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1289.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 733.9±34.3 °C

HET-0016

HET0016 is a potent and selective 20-hydroxyeicosatetraenoic acid (20-HETE) synthase inhibitor, with IC50 values of 17.7 nM, 12.1 nM and 20.6 nM for recombinant CYP4A1-, CYP4A2- and CYP4A3-catalyzed 20-HETE synthesis, respectively. HET0016 also is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth[1][2].

  • CAS Number: 339068-25-6
  • MF: C12H18N2O
  • MW: 206.284
  • Catalog: Cytochrome P450
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 356.9±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 169.7±30.7 °C

Aldose reductase-IN-5

As an aldose reductase (ALR2) inhibitor, the compound is used to enhance the combination of inhibitory excitability and antioxidant capacity to delay the progress of diabetes complications.

  • CAS Number: 2480090-03-5
  • MF: C18H15NO5
  • MW: 325.32
  • Catalog: Aldose Reductase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sodium oxamate

Oxamic acid (oxamate) sodium salt is a lactate dehydrogenase-A (LDH-A) inhibitor. Oxamic acid sodium salt shows anti-tumor activity, and anti-proliferative activity against cancer cells, and can induce apoptosis[1][2][3].

  • CAS Number: 565-73-1
  • MF: C2H2NNaO3
  • MW: 111.032
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 306.3ºC at 760 mmHg
  • Melting Point: 300 °C
  • Flash Point: 139ºC

Dalcetrapib

Dalcetrapib (JTT-705; RO-4607381) is a rhCETP inhibitor with IC50 of 0.2 μM that increases the plasma HDL cholesterol. IC50 value: 0.2 uM [1]Target: CETPin vitro: Dalcetrapib modulates CETP activity. Dalcetrapib induces a conformational change in CETP, when added to human plasma. CETP-induced pre-β-HDL formation in human plasma is unchanged by Dalcetrapib ≤3 μM and increased at 10 μM. Dalcetrapib statistically and significantly increases pre-β-HDL formation [1]. Dalcetrapib achieves 50% inhibition of CETP activity in human plasma at a concentration of 9 μM [2]. Dalcetrapib inhibits the CETP activity of media in HepG2 in a dose-dependent manner [3].in vivo: Treatment with Dalcetrapib leads to significant increases in HDL-C levels. In hamsters injected with [3H]cholesterol-labeled autologous macrophages Dalcetrapib significantly increases fecal elimination of both [3H]neutral sterols and [3H]bile acids. Dalcetrapib increases plasma HDL-[3H]cholesterol [1]. Dalcetrapib has 95% inhibition of CETP activity in male Japanese white rabbits at an oral dose of 30 mg/kg. Dalcetrapib increases the plasma HDL cholesterol level by 27% and 54%, respectively, when given at oral doses of 30 mg/kg or 100 mg/kg once a day for 3 days to male Japanese white rabbits [2].

  • CAS Number: 211513-37-0
  • MF: C23H35NO2S
  • MW: 389.59500
  • Catalog: CETP
  • Density: 1.066 g/cm3
  • Boiling Point: 528.912ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.676ºC

()-trans-C75

(−)-C75 is a isoform of C75 (HY-12364), which is a synthetic fatty-acid synthase (FASN) inhibitor; inhibits prostate cancer cells PC3 with an IC50 of 35 μM[1][2][3]. C75 is a potent CPT1A activator[5].

  • CAS Number: 1234694-22-4
  • MF: C14H22O4
  • MW: 254.32
  • Catalog: Fatty Acid Synthase (FAS)
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 432.1±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 159.2±22.2 °C

MAGL-IN-4

MAGL-IN-4 is an orally active, selective and reversible monoacylglycerol lipase (MAGL) inhibitor with an IC50 of 6.2 nM. MAGL-IN-4 can penetrate the blood-brain barrier (BBB). MAGL-IN-4 enhances endocannabinoid signaling mostly by the increase in the level of 2-AG via selective MAGL inhibition in the brain[1].

  • CAS Number: 2135785-20-3
  • MF: C18H21ClN2O4
  • MW: 364.82
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ramiprilat-d5

Ramiprilat-d5 is deuterium labeled Ramiprilat. Ramiprilat (HOE 498 diacid), an active metabolite of Ramipril, is a potent and orally active angiotensin converting enzyme (ACE) inhibitor with a Ki value of 7 pM. Ramiprilat can be used for high blood pressure and heart failure research[1].

  • CAS Number: 2021255-43-4
  • MF: C21H23D5N2O5
  • MW: 393.49
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Brassinazole

(Rac)-Brassinazole, triazole-type compound, is a brassinosteroid (BR) biosynthesis inhibitor. (Rac)-Brassinazole increases inhibition of CYP90B in BR biosynthesis[1][2]

  • CAS Number: 224047-41-0
  • MF: C18H18ClN3O
  • MW: 327.808
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 533.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.2±32.9 °C

RORγt agonist 4

RORγt agonist 4 (compound 14) is a potent and selective agonist of RORγt. RORγt agonist 4 significantly enhances metabolic stability. RORγt agonist 4 improves the situation of tumor models of mouse B16F10 melanoma and LLC lung adenocarcinoma[1].

  • CAS Number: 2241769-59-3
  • MF: C26H24Cl2N2O4S
  • MW: 531.45
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Benazepril hydrochloride

Benazepril hydrochloride, an angiotensin converting enzyme inhibitor, which is a medication used to treat high blood pressure.Target: angiotensin converting enzyme (ACE)Benazepril hydrochloride is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril hydrochloride is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor [1].Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril hydrochloride group (MB) and evening benazepril hydrochloride group (EB).Benazepril hydrochloride was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril hydrochloride, morning versus evening dosing of benazepril hydrochloride has the same renoprotection effects [2].Clinical indications: Congestive heart failure; End stage renal disease; HypertensionFDA Approved Date: Toxicity: headaches; cough; Anaphylaxis; angioedema; hyperkalemia

  • CAS Number: 86541-74-4
  • MF: C24H29ClN2O5
  • MW: 460.951
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: 691.2ºC at 760 mmHg
  • Melting Point: 188-190°C
  • Flash Point: 371.8ºC

HIV-1 protease-IN-9

HIV-1 protease-IN-9 (compound 5b) is a HIV-1 protease inhibitor, with a Ki of 0.028 nM. HIV-1 protease-IN-9 shows potent antiviral activity, with an IC50 of 66.8 nM[1].

  • CAS Number: 2925381-27-5
  • MF: C37H41N7O4S
  • MW: 679.83
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(3S,5S)-Atorvastatin (sodium salt)

(3S,5S)-Atorvastatin sodium salt is a pregnane X receptor (PXR) activator and the inactive enantiomer of Atorvastatin. Atorvastatin is an orally active HMG-CoA reductase inhibitor with lipid-lowering capabilities[1].

  • CAS Number: 1428118-38-0
  • MF: C33H34FN2NaO5
  • MW: 580.62
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IOX4

IOX4 is a selective HIF prolyl-hydroxylase 2 (PHD2) inhibitor with an IC50 value of 1.6 nM, induces HIFα in cells and in wildtype mice with marked induction in the brain tissue. IOX4 competes with and displaces 2-oxoglutarate (2OG) at the active site of PHD2[1].

  • CAS Number: 1154097-71-8
  • MF: C15H16N6O3
  • MW: 328.326
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 502.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 257.5±32.9 °C

Terlakiren

Terlakiren (CP-80,794) is an orally active inhibitor of renin. Terlakiren inhibits the efficacy of human renin with an IC50 value of 0.7 nM. Terlakiren has potential applications in hypertension[1].

  • CAS Number: 119625-78-4
  • MF: C31H48N4O7S
  • MW: 620.80
  • Catalog: Renin
  • Density: 1.205g/cm3
  • Boiling Point: 908.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 503.1ºC

AHU 377

Sacubitril (AHU-377) is a potent NEP inhibitor with an IC50 of 5 nM. Sacubitril (AHU-377) is a component of the heart failure medicine LCZ696.

  • CAS Number: 149709-62-6
  • MF: C24H29NO5
  • MW: 411.491
  • Catalog: Neprilysin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 656.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.1±31.5 °C

Marimastat (BB-2516)

Marimastat is a broad spectrum inhibitor of MMPs with IC50 values of 3, 5, 6, 9 and 13 nM for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7, respectively.

  • CAS Number: 154039-60-8
  • MF: C15H29N3O5
  • MW: 331.408
  • Catalog: MMP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 148℃
  • Flash Point: N/A

Z-WEHD-FMK

Z-WEHD-FMK is a potent, cell-permeable and irreversible caspase-1/5 inhibitor. Z-WEHD-FMK also exhibits a robust inhibitory effect on cathepsin B activity (IC50=6 μM). Z-WEHD-FMK can be used to investigate cells for evidence of apoptosis[1][2][4].

  • CAS Number: 210345-00-9
  • MF: C37H42FN7O10
  • MW: 763.76900
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cetraxate HCl

Cetraxate hydrochloride (DV-1006), an orally active anti-ulcer agent with mucosal protective effects, can be used for gastric ulcers research[1]. Cetraxate hydrochloride is a potent acrosomal proteinase acrosin inhibitor with a Ki and an IC50 of 0.94 μM and 3.3 μM, respectively[2].

  • CAS Number: 27724-96-5
  • MF: C17H24ClNO4
  • MW: 341.83000
  • Catalog: Ser/Thr Protease
  • Density: 1.182g/cm3
  • Boiling Point: 480.9ºC at 760mmHg
  • Melting Point: 238-240ºC
  • Flash Point: 244.6ºC

Ixazomib (MLN2238)

Ixazomib (MLN2238) is a selective, potent, and reversible proteasome inhibitor, which inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 of 3.4 nM (Ki of 0.93 nM).

  • CAS Number: 1072833-77-2
  • MF: C14H19BCl2N2O4
  • MW: 361.029
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A