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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JTE-151

JTE-151 is a RORγ inhibitor, which can suppress overactive immune response through inhibition of RORγ related to the activation of Th17 cells, making JTE-151 possible to be used in autoimmune disease research[1].

  • CAS Number: 1404380-58-0
  • MF: C28H37ClN2O4
  • MW: 501.06
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrorotenone

Dihydrorotenone, a natural pesticide, is a potent mitochondrial inhibitor. Dihydrorotenone probably induces Parkinsonian syndrome. Dihydrorotenone induces human plasma cell apoptosis by triggering endoplasmic reticulum stress and activating p38 signaling pathway[1].

  • CAS Number: 6659-45-6
  • MF: C23H24O6
  • MW: 396.433
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 553.9±50.0 °C at 760 mmHg
  • Melting Point: 216 °C
  • Flash Point: 241.6±30.2 °C

Bemfivastatin hemicalcium

Bemfivastatin (PPD 10558) hemicalcium is an orally active lipid-lowering agent and HMG-CoA reductase inhibitor. Bemfivastatin hemicalcium enhances the activity of liver extracts. Bemfivastatin hemicalcium has no-observed adverse effect levels (NOAEL) with dosages of ≥320 mg/kg/d (rat developmental toxicity), ≥12.5 mg/kg/d (rabbit maternal toxicity), ≥25 mg/kg/d (rabbit developmental toxicity), respectively. Bemfivastatin hemicalcium can be used in the study of statin-related hypercholesterolemic myalgia in statin-intolerant patients.

  • CAS Number: 805241-64-9
  • MF: C34H37FN2O6.1/2Ca
  • MW: 607.74
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Omarigliptin

Omarigliptin(MK-3102) is a potent, selective and long-acting DPP-4 inhibitor with IC50 of 1.6 nM; highly selective over allproteases tested (IC50 > 67 μM).IC50 value: 1.6 nM [1]Target: DPP-4 inhibitorin vitro: Omarigliptin has weak ion channel activity (IC50 > 30 μM at IKr, Cav1.2, and Nav1.5). An expansive selectivity counterscreen (168 radioligand binding or enzymatic assays) was carried out at MDS Pharma. An IC50 > 10 μM was obtained in all assays. in vivo: When orally administered 1 h prior to dextrose challenge in an oral glucose tolerance test (OGTT), it significantly reduced blood glucose excursion in a dose-dependent manner from 0.01 mg/kg (7% reduction in glucose AUC) to 0.3 mg/kg (51% reduction).

  • CAS Number: 1226781-44-7
  • MF: C17H20F2N4O3S
  • MW: 398.427
  • Catalog: Dipeptidyl Peptidase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 529.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.0±32.9 °C

MMP Inhibitor II

MMP Inhibitor II (compound 4e) is a potent, reversible pan-MMP inhibitor with IC50 values of 24 nM, 18.4 nM, 30 nM, and 2.7 nM for MMP-1,MMP-3, MMP-7, and MMP-9, respectively[1].

  • CAS Number: 203915-59-7
  • MF: C21H27N3O8S2
  • MW: 513.584
  • Catalog: MMP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cbl-b-IN-9

Cbl-b-IN-9 (Compound 300) is a casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl inhibitor with IC50s of 5.6 nM and 4.7 nM, respectively[1].

  • CAS Number: 2815223-41-5
  • MF: C30H33F3N6O2
  • MW: 566.62
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RORγt inverse agonist 23

RORγt inverse agonist 23 is a potent, selective, and orally available novel retinoic acid receptor-related orphan receptor γt inverse agonist.

  • CAS Number: 2230779-18-5
  • MF: C26H33NO5S
  • MW: 471.61
  • Catalog: ROR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxycycline

Doxycycline, an antibiotic, is an orally active and broad-spectrum metalloproteinase (MMP) inhibitor[1].

  • CAS Number: 564-25-0
  • MF: C22H24N2O8
  • MW: 444.435
  • Catalog: MMP
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 685.2±55.0 °C at 760 mmHg
  • Melting Point: 206-209ºC
  • Flash Point: 368.2±31.5 °C

Sildenafil Mesylate

Sildenafil Mesylate is an orally active and selective phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil Mesylate can be used in studies of erectile dysfunction and cancer[1].

  • CAS Number: 1308285-21-3
  • MF: C23H34N6O7S2
  • MW: 570.68
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TK05

TK05 is a potent and selective inhibitor of leukotriene C4 synthase (LTC4S) with an IC50 of 95 nM[1].

  • CAS Number: 1245734-61-5
  • MF: C31H25ClN2O5
  • MW: 540.99
  • Catalog: Gutathione S-transferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MGAT2-IN-1

MGAT2-IN-1 is an orally active inhibitor of monoacylglycerol acyltransferase (MGAT2) with IC50 of 7.8 and 2.4 nM for human and mouse MGAT2, respectively.

  • CAS Number: 1800025-30-2
  • MF: C27H21ClF5N7O3S
  • MW: 654.01
  • Catalog: Acyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monomyristin

1-Monomyristin, extracted from Serenoa repens, inhibits the hydrolysis of 2-oleoylglycerol (IC50=32 μM) and fatty acid amide hydrolase (FAAH) activity (IC50=18 μM). 1-Monomyristin shows antibacterial activity against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans and also antifungal activity against Candida albicans[1][2][3].

  • CAS Number: 589-68-4
  • MF: C17H34O4
  • MW: 302.449
  • Catalog: Bacterial
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 424.8±25.0 °C at 760 mmHg
  • Melting Point: 68-70ºC
  • Flash Point: 141.3±16.7 °C

Chetoseminudin B

Chetoseminudin B possesses mushroom tyrosinase inhibitory activity with IC50 of 31.7 μM[1].

  • CAS Number: 658711-87-6
  • MF: C17H21N3O3S2
  • MW: 379.50
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OBAA

(2E)-OBAA is a potent phospholipase A2 (PLA2) inhibitor, with an IC50 of 70 nM. (2E)-OBAA induces apoptosis of HUVEC cells. (2E)-OBAA blocks Melittin-induced Ca2+ influx in Trypanosoma brucei, with an IC50 of 0.4 μM[1][2][3][4].

  • CAS Number: 221632-26-4
  • MF: C28H44O3
  • MW: 428.647
  • Catalog: Apoptosis
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 558.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.7±26.6 °C

Tautomycin

Tautomycin, an antifungal antibiotic isolated from the bacterium Streptomyces verticillatus, is a potent and specific inhibitor of protein phosphatases 1 and 2A and induces contraction of smooth muscle under Ca2+-free conditions, with Kiapp values of 0.16 nM and 0.4 nM for PP1 and PP2A, respectively[1][2].

  • CAS Number: 109946-35-2
  • MF: C41H66O13
  • MW: 766.95500
  • Catalog: Phosphatase
  • Density: 1.18g/cm3
  • Boiling Point: 854.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 247.5ºC

Acetylarenobufagin

Acetylarenobufagin is a steroidal hypoxia inducible factor-1 (HIF-I) modulator[1].

  • CAS Number: 184673-79-8
  • MF: C26H34O7
  • MW: 458.54
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: 1.31±0.1 g/cm3(Predicted)
  • Boiling Point: 634.8±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Rovunaptabin

Rovunaptabin (ARC 183) is a DNA aptamer, which is a single-stranded DNA molecule consisting of 15 deoxynucleotides that forms well-defined three-dimensional configuration, allowing it to bind to thrombin with high affinity and specificity.

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

LU-002i

LU-002i is a subunit-selective human proteasome β2c and β2i inhibitor with an IC50 value of 220 nM for β2i[1].

  • CAS Number: 1838705-22-8
  • MF: C35H52N4O7
  • MW: 640.81
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Varespladib sodium

Varespladib sodium (LY315920 sodium) is a potent and selective group IIA, secretory phospholipase A2 (sPLA2) inhibitor with an IC50 of 9 nM. Varespladib sodium exhibits the significant inhibitory effect on sPLA2 activity in serum from various species including rat, rabbit, guinea pig and human with IC50s of 8.1 nM, 5.0 nM, 3.2 nM and 6.2 nM, respectively[1].

  • CAS Number: 172733-42-5
  • MF: C21H19N2NaO5
  • MW: 402.37600
  • Catalog: Phospholipase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mca-Pro-β-cyclohexyl-Ala-Gly-Nva-His-Ala-Dap(Dnp)-NH2 trifluoroacetate salt

Mca-P-Cha-G-Nva-HA-Dap(DNP)-NH2 is a fluorogenic substrate for matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-26. Mca-P-Cha-G-Nva-HA-Dap(DNP)-NH2 can be used to quantify MMP-1, MMP-3 and MMP-26 activity[1][2].

  • CAS Number: 256394-94-2
  • MF: C51H65N13O15
  • MW: 1100.14000
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginsenoside F1

Ginsenoside F1, an enzymatically modified derivative of Ginsenoside Rg1, demonstrates competitive inhibition of CYP3A4 activity and weaker inhibition of CYP2D6 activity.

  • CAS Number: 53963-43-2
  • MF: C36H62O9
  • MW: 638.872
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 751.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 408.4±32.9 °C

Trifolirhizin

Trifolirhizin is a pterocarpan flavonoid isolated from the roots of Sophora flavescens. Trifolirhizin possesses potent tyrosinase inhibitory activity with an IC50 of 506 μM[1]. Trifolirhizin exhibits potential anti-inflammatory and anticancer activities[2].

  • CAS Number: 6807-83-6
  • MF: C22H22O10
  • MW: 446.404
  • Catalog: Tyrosinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 658.7±55.0 °C at 760 mmHg
  • Melting Point: 142-144ºC
  • Flash Point: 352.2±31.5 °C

ONO 4817

ONO-4817 is a potent inhibitor of matrix metalloproteinase (MMP). Inhibition of matrix metalloproteinases (MMPs) is expected to suppress atherosclerotic neointimal proliferation and thus limits atheromatous plaque progression. ONO-4817 suppresses the development of aortic intimal hyperplasia in experimental hyperlipidemic rabbit[1].

  • CAS Number: 223472-31-9
  • MF: C22H28N2O6
  • MW: 416.46800
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AGN 193109

AGN 193109 is a retinoid analog, and acts as a specific and highly effective antagonist of retinoic acid receptors (RARs), with Kds of 2 nM, 2 nM, and 3 nM for RARα, RARβ, and RARγ, respectively.

  • CAS Number: 171746-21-7
  • MF: C28H24O2
  • MW: 392.48900
  • Catalog: RAR/RXR
  • Density: 1.21 g/cm3
  • Boiling Point: 564.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 257.1ºC

h15-LOX-2 inhibitor 1

h15-LOX-2 inhibitor 1 (Comp 105) is a human epithelial 15-lipoxygenase-2 (h15-LOX-2) inhibitor with IC50 of 0.34 μM[1].

  • CAS Number: 478040-08-3
  • MF: C17H13F3N2S
  • MW: 334.36
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uralenol

Uralenol is a natural PTP1B inhibitor (IC50=21. 5 μM) from Broussonetia papyrifera. PTP1B have been shown to play a major role in the dephosphorylation of the insulin receptor in many cellular and biochemical studies[1].

  • CAS Number: 139163-15-8
  • MF: C20H18O7
  • MW: 370.35300
  • Catalog: Phosphatase
  • Density: 1.519g/cm3
  • Boiling Point: 654.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 236.6ºC

ALDH3A1-IN-1

ALDH3A1-IN-1 (Compound 18) is a potent inhibitor of ALDH3A1 with an IC50 of 1.61 μM. ALDH3A1-IN-1 is more potent than DEAB against patient-derived primary prostate tumor epithelial cells, as single agents or in combination treatment with docetaxel[1].

  • CAS Number: 1039855-56-5
  • MF: C13H18N2O3
  • MW: 250.29
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CEP-18770 (Delanzomib)

Delanzomib(CEP-18770) is a novel orally-active inhibitor of the chymotrypsin-like activity of the proteasome that down-modulates the nuclear factor-kappaB (NF-kappaB) activity.IC50 Value: 3.8 nM [1]Target: proteasomein vitro: CEP-18770 and bortezomib showed comparable potency against chymotrypsin-like proteasome activity, cellular inhibitory activity (IC50) values of 3.8 (± 1.0) nM and 3.8 (± 0.4) nM, respectively, CEP-18770 had a 2- to 11-fold lower cytotoxic potency compared with bortezomib against solid tumor cell lines, comparable potency against 2 hematologic tumor cell lines, and a similar spectrum of antiproliferative activity with IC50 values for both compounds of less than 35 nM [1].in vivo: in MM xenograft models, the addition of CEP-18770 IV to melphalan completely prevented the growth of both melphalan-sensitive and melphalan-resistant tumours. The combination of CEP-18770 IV and bortezomib induced complete regression of bortezomib-sensitive tumours and markedly delayed progression of bortezomib-resistant tumours compared to treatment with either agent alone [2]. Age matched MRL/lpr or NZBWF1 mice with established SLE or LN, respectively, were treated with delanzomib either 3 mg/kg once or twice weekly intravenously or orally at 10 mg/kg [3]. Toxicity: CEP-18770 showed a favourable safety profile with lack of neurotoxicity and linear plasma PK. The definition of the optimal biological dose and schedule of treatment is actively pursued because of the high incidence of skin toxicity of the twice a week schedule [4].Clinical trial: CEP-18770 in Combination With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. Phase1/2

  • CAS Number: 847499-27-8
  • MF: C21H28BN3O5
  • MW: 413.275
  • Catalog: Proteasome
  • Density: 1.207
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RKLLW-NH2

RKLLW-NH2 is a Cathepsin L inhibitor[1].

  • CAS Number: 289480-71-3
  • MF: C35H59N11O5
  • MW: 713.91
  • Catalog: Cathepsin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A37

CM037 is a selective inhibitor of ALDH1A1 (aldehyde dehydrogenase 1A1) with an IC50 of 4.6 µM[1].

  • CAS Number: 896795-60-1
  • MF: C21H25N3O3S2
  • MW: 431.572
  • Catalog: Aldehyde Dehydrogenase (ALDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A