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.


Anti-infection >
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Metabolic Enzyme/Protease >
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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NSC689857

NSC689857 is a potent EGFR and SCFSKP2 inhibitor with an IC50 value of 36 μM for Skp2-Cks1. NSC689857 can inhibit p27 ubiquitylation (IC50=30 μM). NSC689857 has varied activity across cancer types, with more activity against leukemia cell lines than others[1][2].

  • CAS Number: 241127-79-7
  • MF: C25H29NO4
  • MW: 407.50
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HI5

HI5 is a potent tublin and IDO inhibitor, with an IC50 value of 70 nM in HeLa cells. HI5 inhibit IDO expression and decrease kynurenine production, leading to stimulating T cells activation and proliferation. HI5 can inhibit tubulin polymerization and cell migration, cause G2/M phase arrest, and induce apoptosis via the mitochondrial dependent apoptosis pathway and cause reactive oxidative stress generation in HeLa cells. HI5 can be used for researching anticancer[1].

  • CAS Number: 2411548-90-6
  • MF: C42H43N5O8
  • MW: 745.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deltarasin

Deltarasin hydrochloride is an inhibitor of KRAS-PDEδinteraction with Kd of 38 nM for binding to purified PDEδ.

  • CAS Number: 1440898-82-7
  • MF: C40H38ClN5O
  • MW: 640.216
  • Catalog: Ras
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Prolyl Hydroxylase inhibitor 1

Prolyl Hydroxylase inhibitor 1 (Compound 15i) is an orally active hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor with an IC50 of 62.23 nM[1]. Antianemia agent[1].

  • CAS Number: 2205125-60-4
  • MF: C19H18ClN5O4
  • MW: 415.83
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML299

ML299 is a potent, CNS penetrant, dual phospholipase PLD1/PLD2 probe with IC50 of 6 nM/20 nM, respectively; robustly increases caspase 3/7 activation under serum-free conditions, provides a dose-dependent decrease (100 nM to 10 uM) in invasive migration in U87-MG cells, with statistical significance reached at both the 1 uM and 10 uM doses.

  • CAS Number: 1426916-00-8
  • MF: C23H26BrFN4O2
  • MW: 489.380
  • Catalog: Phospholipase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 708.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.5±32.9 °C

Alicapistat

Alicapistat (ABT-957) is an orally active selective inhibitor of human calpains 1 and 2 for the potential use in the treatment of Alzheimer's disease (AD).

  • CAS Number: 1254698-46-8
  • MF: C25H27N3O4
  • MW: 433.50
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1S,2S)-Bortezomib

(1S,2S)-Bortezomib is an enantiomer of Bortezomib. Bortezomib is a cell-permeable, reversible, and selective proteasome inhibitor, and potently inhibits 20S proteasome (Ki of 0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is an anti-cancer agent and the first therapeutic proteasome inhibitor to be used in humans[1][2][3].

  • CAS Number: 1132709-14-8
  • MF: C19H25BN4O4
  • MW: 384.237
  • Catalog: Proteasome
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mitochonic acid 5

Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage. Mitochonic acid 5 modulates mitochondrial ATP synthesis.

  • CAS Number: 1354707-41-7
  • MF: C18H13F2NO3
  • MW: 329.30
  • Catalog: Mitochondrial Metabolism
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fluvastatin

Fluvastatin (Leschol) inhibits HMG-CoA reductase activity with IC50 of 8 nM.IC50 value: 8 nMTarget: HMG-CoA reductaseFluvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMGCR), the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Human hepatocellular carcinoma cell (HCC) studies indicate that Fluvastatin induces G2/M phase arrest. In the presence of Fluvastatin, HCC cells show a decrease of Bcl-2 and procaspase-9 expression, and an increase in Bax, cleaved caspase-3, and cytochrome c. Fluvastatin is antilipemic and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

  • CAS Number: 93957-54-1
  • MF: C24H26FNO4
  • MW: 411.466
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 681.8±55.0 °C at 760 mmHg
  • Melting Point: 194-197ºC
  • Flash Point: 366.1±31.5 °C

CM 10

CM10 is a potent and selective aldehyde dehydrogenase 1A family inhibitor (ALDH1Ai), with IC50s of 1700, 740, and 640 nM for ALDH1A1, ALDH1A2, and ALDH1A3, respectively. CM10 does not inhibit any of the other ALDH family members. CM10 can regulate metabolism and has anti-cancer activity[1].

  • CAS Number: 692269-09-3
  • MF: C20H23N3O
  • MW: 321.42
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: 1.12±0.1 g/cm3(Predicted)
  • Boiling Point: 512.4±52.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

HA 130

HA130 is a selective ATX (autotaxin) inhibitor with IC50 of 28 nM. IC50 value: 28 nM [2]Target: ATXin vitro: HA130 completely blocks the ability of ATX to promote TEM (transendothelial migration). HA130 at 0.3 μM completely ablates the activity of ATX on TK1 uropod formation. [1]in vivo: HA130 instantaneously lowers plasma levels of LPA in mice after intravenous administration. HA130 is an inhibitor of the enzymatic activity of ATX, slows T cell migration across lymph node HEVs. HA130 decreased the "outside HEVs/inside HEVs" ratio by 3-4-fold, compared to vehicle-treated animals vehicle (p < 0.01 for both PLNs and MLNs). [1]

  • CAS Number: 1229652-21-4
  • MF: C24H19BFNO5S
  • MW: 463.28600
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methyl-2-butenoic acid [8-hydroxymethyl-1,5-dimethyl-5-(4-methyl-3-pentenyl)-12-oxabicyclo[9.1.0]dodeca-3,7-dien-2-yl] ester

Vibsanin A, a protein kinase C (PKC) activator, exhibits anti-proliferative activity against human cancer cell lines. Vibsanin A is also a HSP90 inhibitor[1].

  • CAS Number: 72506-14-0
  • MF: C25H38O4
  • MW: 402.57
  • Catalog: HSP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 501.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 158.5±23.6 °C

ENPP1 Inhibitor C

Enpp-1-IN-2 (Compound C) is a potent ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) inhibitor with IC50 values of 0.26, 0.48 and 2.0 μM evaluated by means of TG-mAMP, pNP-TMP, and ATP assays, respectively. TG (Tokyo Green)-mAMP: a newly synthesized sensitive ENPP1 fluorescence probe[1].

  • CAS Number: 2378640-92-5
  • MF: C15H18N6
  • MW: 282.344
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aliskiren D6 Hydrochloride

Aliskiren D6 Hydrochloride is is deuterium labeled Aliskiren, which is a direct renin inhibitor with IC50 of 1.5 nM.

  • CAS Number: 1246815-96-2
  • MF: C30H48D6ClN3O6
  • MW: 594.26
  • Catalog: Renin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Frovocimab

Frovocimab (LY 3015014) is a humanized IgG4 monoclonal antibody (mAb) that neutralizes PCSK9. Frovocimab inhibits PCSK9 binding to LDL receptor (LDLR) while permitting the normal proteolytic cleavage of the bound intact PCSK9[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enpp-1-IN-14

ENPP1-IN-2 is a potent Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1) inhibitor with an IC50 value of 32.38 nM for recombinant human ENPP-1. ENPP1-IN-2 has anti-tumor activity[1].

  • CAS Number: 2687222-59-7
  • MF: C15H22ClN5O4S
  • MW: 403.88
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoastilbin

Isoastilbin is a dihydroflavonol glycoside compound in Rhizoma Smilacis glabrae and Astragalus membranaceus. Isoastilbin inhibits glucosyltransferase (GTase) with an IC50 value of 54.3 μg/mL, and also inhibits tyrosinase activity. Isoastilbin shows neuroprotective, antioxidation, antimicrobial and anti-apoptotic properties and has the potential for Alzheimer’s disease research[1][21][3].

  • CAS Number: 54081-48-0
  • MF: C21H22O11
  • MW: 450.393
  • Catalog: Bacterial
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 801.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.9±27.8 °C

Rosuvastatin D3 Sodium

Rosuvastatin D3 Sodium is deuterium labeled Rosuvastatin, which is a competitive inhibitor of HMG-CoA reductase with IC50 of 11 nM.

  • CAS Number: 1279031-70-7
  • MF: C22H24D3FN3NaO6S
  • MW: 506.53800
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >76°C (分解)
  • Flash Point: N/A

Ganodermanondiol

Ganodermanondiol is a melanogenesis inhibitor isolated from the Ganoderma lucidum[1].Ganodermanondiol exhibits potent cytoprotective effects on tert-butyl hydroperoxide-induced hepatotoxicity[2]. Ganodermanondiol shows significant anti-HIV-1 protease activity with an IC50 of 90 μM[3]. Ganodermanondiol exhibits a strong anticomplement activity against the classical pathway of the complement system with an IC50 of 41.7μM[4].

  • CAS Number: 107900-76-5
  • MF: C30H48O3
  • MW: 456.700
  • Catalog: HIV Protease
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 580.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 318.9±26.6 °C

Brinzolamide

Brinzolamide(AL 4862) is a potent carbonic anhydrase II inhibitor with IC50 of 3.19 nM.Target: carbonic anhydrase IIBrinzolamide (< 1 mg) ophthalmic suspension lowers intraocular pressure in Dutch-belted pigmented rabbits in a dose-dependent manner with an onset within 0.5 hour and a peak response by 1-2 hours. Brinzolamide (0.6 mg) ophthalmic suspension lowers intraocular pressure in laser-treated glaucomatous cynomolgus monkeys in a dose-dependent manner with an onset within 1 hour and a peak response by 3 hours. Brinzolamide dosages of 30 mg/kg, produces a 44% reduction in intestinal charcoal meal progression, but 1 and 10 mg/kg produced 8% and 18% decreases, respectively, in male CD-1 mice. Brinzolamide of 1 mg/kg, 10 mg/kg, and 30 mg/kg prolongs barbiturate sleep time by 57%, 15%, and 35%, respectively, in male CD-1 mice [1]. Brinzolamide (< 3%) produces significantly greater mean percent intraocular pressure reductions and mean intraocular pressure reductions compared with placebo in patients with primary, open-angle glaucoma or ocular hypertension. The optimal intraocular pressure-lowering concentration of brinzolamide is 1%, brinzolamide 1% is well tolerated by patients with primary open-angle glaucoma or ocular hypertension when administered twice daily [2].

  • CAS Number: 138890-62-7
  • MF: C12H21N3O5S3
  • MW: 383.507
  • Catalog: Carbonic Anhydrase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 586.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.2±32.9 °C

IDO1-IN-22

IDO1-IN-22 (Compound 3) is a IDO1 inhibitor (biochemical hIDO1 IC50: 67.4 nM, HeLa hIDO1 IC50: 17.6 nM). IDO1-IN-22 has excellent antitumor efficacy in LLC xenograft model, as well as desirable pharmacokinetic (PK) profile[1].

  • CAS Number: 2126853-16-3
  • MF: C12H12BrFN6O3
  • MW: 387.16
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epacadostat(INCB024360)

Epacadostat (INCB 024360) is a potent and selective indoleamine 2,3-dioxigenase 1 (IDO1) inhibitor with an IC50 of 71.8 nM.

  • CAS Number: 1204669-58-8
  • MF: C11H13BrFN7O4S
  • MW: 438.233
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 672.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 360.4±34.3 °C

BI8626

BI8626 is a specific inhibitor of the ubiquitin ligase HUWE1 with an IC50 of 0.9 μM[1].

  • CAS Number: 1875036-75-1
  • MF: C25H28N8
  • MW: 440.54
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Atorvastatin Sodium

Atorvastatin sodium is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids. Atorvastatin sodium inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 μM and 2.39 μM, respectively[1][2][3][4][5].

  • CAS Number: 134523-01-6
  • MF: C33H34FN2NaO5
  • MW: 580.62
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 722.2±60.0ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.6±32.9ºC

Prenyl-IN-1

Prenyl-IN-1 is a protein prenylation inhibitor, especially a geranylgeranyltransferase (GGT) or a farnesyltransferase (FT) inhibitor, exhibiting potent activity against oxidative stress, and particularly in the treatment of Parkinson's Disease.

  • CAS Number: 360561-53-1
  • MF: C28H24ClN5O2
  • MW: 497.98
  • Catalog: Farnesyl Transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAP-I

Speract, a sea urchin egg peptide that regulates sperm motility, also stimulates sperm mitochondrial metabolism.

  • CAS Number: 76901-59-2
  • MF: C38H57N11O14
  • MW: 891.92400
  • Catalog: Peptides
  • Density: 1.337g/cm3
  • Boiling Point: 1502.321ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 862.373ºC

MAO A/HSP90-IN-1

MAO A/HSP90-IN-1 (4-b) is a MAO A/HSP90 dual inhibitor with IC50 value of 1.77 μM and 0.019 μM in Glioblastoma (GBM) GL26 cells and HSP90α, respectively. MAO A/HSP90-IN-1 (4-b) can inhibit MAO A activity, HSP90 binding and the expression of HER2 and phospho-Akt to inhibit the growth of GBM, they also reduce PD-L1 expression, which inhibits T cell activation. MAO A/HSP90-IN-1 (4-b) have potential to inhibit tumor immune escape. MAO A/HSP90-IN-1 (4-b) can be used for brain tumor-related diseases research[1].

  • CAS Number: 2927489-95-8
  • MF: C24H29ClN2O4
  • MW: 444.95
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

116-9e

116-9e (MAL2-11B) is a Hsp70 co-chaperone DNAJA1 inhibitor. 116-9e inhibits Simian Virus 40 (SV40) replication and DNA synthesis. 116-9e inhibits tumor antigen (TAg)’s endogenous ATPase activity and the TAg-mediated activation of Hsp70[1][2].

  • CAS Number: 831217-43-7
  • MF: C31H32N2O5
  • MW: 512.60
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Perindoprilat

Perindoprilat (S 9780) is an angiotensin-converting enzyme (ACE) inhibitor with the IC50 value ranging from 1.5 to 3.2 nM. Perindoprilat can be used in hypertension research[1][2].

  • CAS Number: 95153-31-4
  • MF: C17H28N2O5
  • MW: 340.415
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 568.1±45.0 °C at 760 mmHg
  • Melting Point: 153-155ºC
  • Flash Point: 297.4±28.7 °C

NU223612

NU223612 is a potent PROTAC (PROTACs) that degrades indoleamine 2,3-dioxygenase 1 (IDO1) (Indoleamine 2,3-Dioxygenase (IDO)) with a Kd of 640 nM. NU223612 potently degrades the IDO1 protein through CRBN-mediated proteasomal degradation. NU223612 is bound to CRBN with an affinity of 290 nM. NU223612 can cross the blood-brain barrier (BBB)[1].

  • CAS Number: 2759420-43-2
  • MF: C49H55FN6O9
  • MW: 890.99
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A