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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STF 118804

STF-118804 is a highly specific NAMPT inhibitor; reduces the viability of most B-ALL cell lines with IC50 <10 nM.IC50 value:Target: NAMPT inhibitorin vitro: improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and targets leukemia stem cells. STF-118804 displays distinctive cytotoxicity by inducing apoptosis without causing a phase-specific cell cycle arrest. Over-expression of NAMPT rendered 293T cells more resistant to STF-118804 resulting in a higher IC50 (106 nM, 95% CI 74–151 nM) compared to control cells (17 nM, 95% CI 13–23 nM), further confirming that NAMPT protein levels dictate sensitivity to STF-118804 [1].in vivo: STF-118804 displayed high efficacy in a xenograft model of ALL. Mice treated with STF-118804 over a 20-day period survived an average of 34 days longer than vehicle-treated animals. During treatment, bioimaging showed regression of tumor followed by suppression of disease. STF-118804 was tolerated in the efficacious dose range, and the absence of adverse physical or pathological effects indicated that toxicity was not limiting in a 20-day study of mock transplanted mice [1].

  • CAS Number: 894187-61-2
  • MF: C25H23N3O4S
  • MW: 461.533
  • Catalog: Nampt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1H-Naphtho(2,3-d)-1,2,3-triazole-4,9-dione, 1-phenyl-

IDO1/TDO-IN-2 (Compound 1) is a potent inhibitor of IDO1/TDO with IC50s of 0.1 and 0.07 μM. IDO1/TDO-IN-2 has the potential for the research of cancer diseases[1].

  • CAS Number: 5466-47-7
  • MF: C16H9N3O2
  • MW: 275.26
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: 1.44g/cm3
  • Boiling Point: 523.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 270.3ºC

Tiplaxtinin

Tiplaxtinin is a selective and orally efficacious inhibitor of plasminogen activator inhibitor-1 (PAI-1) with IC50 of 2.7 μM.

  • CAS Number: 393105-53-8
  • MF: C24H16F3NO4
  • MW: 439.383
  • Catalog: PAI-1
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 588.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 309.4±30.1 °C

4,4'-Carbonyldiphthalic acid

Benzophenonetetracarboxylic acid can inprove activity and stability of alkaline phosphatases from psychrophilic and mesophilic organisms.Benzophenonetetracarboxylic acid can improve activity and stability of alkaline phosphatases from psychrophilic and mesophilic organisms by chemically modifying aliphatic or amino groups

  • CAS Number: 2479-49-4
  • MF: C17H10O9
  • MW: 358.256
  • Catalog: Phosphatase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 734.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 411.7±29.4 °C

Saquinavir-d9

Saquinavir-d9 (Ro 31-8959-d9) is the deuterium labeled Saquinavir. Saquinavir(Ro 31-8959) is an HIV Protease inhibitor used in antiretroviral therapy. Saquinavir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 1.36 μM[1][2].

  • CAS Number: 1356355-11-7
  • MF: C38H41D9N6O5
  • MW: 679.89600
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deoxyneocryptotanshinone

Deoxyneocryptotanshinone, a natural tanshinone, is a high affinity BACE1 (Beta-secretase) inhibitor with an IC50 value of 11.53 μM. Deoxyneocryptotanshinone shows a promising dose-dependent inhibition of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 133.5 μM. Deoxyneocryptotanshinone can be used for Alzheimer's disease research[1][2].

  • CAS Number: 27468-20-8
  • MF: C19H22O3
  • MW: 298.376
  • Catalog: Phosphatase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 468.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.0±25.2 °C

KT203

KT203 is a potent and selective inhibitor of α/β-hydrolase domain containing 6 (ABHD6), with an IC50 of 0.31 nM in Neuro2A cells[1].

  • CAS Number: 1402612-64-9
  • MF: C28H26N4O3
  • MW: 466.53
  • Catalog: MAGL
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Tyrosine-d2

D-Tyrosine-d2 is the deuterium labeled D-Tyrosine. D-Tyrosine is the D-isomer of tyrosine. D-Tyrosine negatively regulates melanin synthesis by inhibiting tyrosinase activity. D-Tyrosine inhibits biofilm formation and trigger the self-dispersal of biofilms without suppressing bacterial growth[1][2].

  • CAS Number: 1202064-22-9
  • MF: C9H9D2NO3
  • MW: 183.20
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-Hydroxybenzbromarone

6-Hydroxybenzbromarone is the major metabolite of Benzbromarone with a longer half-life and greater pharmacological potency than the parent compound. 6-Hydroxybenzbromarone is a protein Eyes Absent 3 (EYA3) inhibitor with an IC50 value of 21.5 μM. 6-Hydroxybenzbromarone is an angiogenic agent, has strong inhibitory effects on cell migration, tubulogenesis, and angiogenic sprouting[1].

  • CAS Number: 152831-00-0
  • MF: C17H12Br2O4
  • MW: 440.08300
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Maraniol

7-Ethoxy-4-methylcoumarin is a coumarin derivative and can be used as a substrate probe of mammalian cytochromes P450 1A1, 2B4 and 2B6[1][2].

  • CAS Number: 87-05-8
  • MF: C12H12O3
  • MW: 204.222
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 351.4±37.0 °C at 760 mmHg
  • Melting Point: 114-116 °C(lit.)
  • Flash Point: 146.2±21.1 °C

α-lytic endopeptidase

From the myxobacterium Lysobacter enzymogenes. In peptidase family S1 (trypsin family) Reaction: Preferential cleavage: Ala┼, Val┼ in bacterial cell walls, elastin and other proteins

  • CAS Number: 37288-76-9
  • MF:
  • MW:
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tigulixostat

Tigulixostat is a novel (indolyl)heteroarylcarboxylate derivatives effective as non-purine selective xanthine oxidase inhibitor, which lowers the production of uric acid[1].

  • CAS Number: 1287766-55-5
  • MF: C16H14N4O2
  • MW: 294.31
  • Catalog: Xanthine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Hydroxyferulic acid

5-Hydroxyferulic acid is a hydroxycinnamic acid and is a metabolite of the phenylpropanoid pathway. 5-Hydroxyferulic acid is a precursor in the biosynthesis of sinapic acid and is also a COMT non-esterifed substrate[1][2][3].

  • CAS Number: 1782-55-4
  • MF: C10H10O5
  • MW: 210.18300
  • Catalog: COMT
  • Density: 1.44g/cm3
  • Boiling Point: 449.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 182.8ºC

Galangin

Galangin is an agonist/antagonist of the arylhydrocarbon receptor, and also shows inhibition of CYP1A1 activity.

  • CAS Number: 548-83-4
  • MF: C15H10O5
  • MW: 270.237
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 518.6±50.0 °C at 760 mmHg
  • Melting Point: 214-215 °C(lit.)
  • Flash Point: 202.0±23.6 °C

AGN 195183

AGN 195183 is a potent and selective agonist of RARα(Kd=3 nM) with improved binding selectivity relative to AGN 193836; no activity on RARβ/γ.IC50 value: 3 nM (Kd); 200 nM (EC80, RAR Trans.)Target: RARα agonistCompound 4(AGN-195183) inhibited the growth of breast cancer cell lines, and was inactive in an in vivo model of topical irritation.Compound 4 and ATRA inhibit growth of the human breast cancer cell lines, T-47D and SK-BR-3, compound 4 does not cause the topical irritation induced by the RARa-selective retinoid, Am-580. Compound 4 (AGN 195183) is currently in Phase I/IIA clinical trials in cancer patients.

  • CAS Number: 367273-07-2
  • MF: C22H22ClF2NO4
  • MW: 437.864
  • Catalog: RAR/RXR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 500.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 256.7±30.1 °C

(Rac)-5-Keto Fluvastatin

(Rac)-5-Keto Fluvastatin (3-Hydroxy-5-Keto Fluvastatin) is an impurity of Fluvastatin (XU 62320). Fluvastatin is a HMG-CoA reductase inhibitor with an IC50 of 8 nM[1].

  • CAS Number: 1160169-39-0
  • MF: C24H24FNO4
  • MW: 409.45000
  • Catalog: HMG-CoA Reductase (HMGCR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sacubitrilat

Sacubitrilat is an active neprilysin (NEP) inhibitor.

  • CAS Number: 149709-44-4
  • MF: C22H25NO5
  • MW: 383.43800
  • Catalog: Neprilysin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(-)-Hydroxycitric acid

(-)-Hydroxycitric acid (Garcinia acid) is the principal acid of fruit rinds of Garcinia cambogia. (-)-Hydroxycitric acid is a potent and competitive inhibitor of ATP citrate lyase. (-)-Hydroxycitric acid suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss[1][2].

  • CAS Number: 27750-10-3
  • MF: C6H8O8
  • MW: 530.43200
  • Catalog: ATP Citrate Lyase
  • Density: 1.947g/cm3
  • Boiling Point: 393.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 205.8ºC

hCAXII-IN-2

hCAXII-IN-2 (compound 5i) is a potent human carbonic anhydrase XII (hCA XII) and hCA IX inhibitor with Ki values of 84.2 nM and 268.5 nM, respectively. hCAXII-IN-2 shows less active against hCA I and hCA II[1].

  • CAS Number: 2497504-86-4
  • MF: C21H18ClN3O4
  • MW: 411.84
  • Catalog: Carbonic Anhydrase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SR1078

SR1078 is an agonist of retinoic acid receptor-related orphan receptor α/γ (RORα/RORγ).

  • CAS Number: 1246525-60-9
  • MF: C17H10F9NO2
  • MW: 431.252
  • Catalog: ROR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 362.9±42.0 °C at 760 mmHg
  • Melting Point: 169℃
  • Flash Point: 173.3±27.9 °C

PF-05085727

PF-05085727 is a potent, selective and brain penetrant Phosphodiesterase 2A (PDE2A) inhibitor with an IC50 of 2 nM.

  • CAS Number: 1415637-72-7
  • MF: C20H18F3N7
  • MW: 413.40
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-SBFI-26

(S)-SBFI-26 is the (S) enantiomer of SBFI-26, an anti-nociceptive agent binds to anandamide transporters FABP5 and FABP7. (S)-SBFI-26 has anti-nociceptive and anti-inflammatory effects[1].

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

Ursodeoxycholic acid-13C

Ursodeoxycholic acid-13C is the 13C labeled Ursodeoxycholic acid. Ursodeoxycholic acid (Ursodeoxycholate) is a secondary bile acid issued from the transformation of (cheno)deoxycholic acid by intestinal bacteria, acting as a key regulator of the intestinal barrier integrity and essential for lipid metabolism. Ursodeoxycholic acid acts as signaling molecule, exerting its effects by interacting with bile acid activated receptors, including G-protein coupled bile acid receptor 5 (TGR5, GPCR19) and the farnesoid X receptor (FXR). Ursodeoxycholic acid can be used for the research of a variety of hepatic and gastrointestinal diseases. Orally active[1][2].

  • CAS Number: 63296-46-8
  • MF: C2313CH40O4
  • MW: 393.56
  • Catalog: GPCR19
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

U73122

U-73122 is an inhibitor of phospholipase C (PLC), phospholipase A2, and 5-LO (5-lipoxygenase).

  • CAS Number: 112648-68-7
  • MF: C29H40N2O3
  • MW: 464.639
  • Catalog: 5-Lipoxygenase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 617.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.0±31.5 °C

HDAC/HSP90-IN-3

HDAC/HSP90-IN-3 (compound J5) is a potent and selective fungal Hsp90 and HDAC dual inhibitor, with IC50 values of 0.83 and 0.91 μM, respectively. HDAC/HSP90-IN-3 shows antifungal activity against azole resistant C. albicans. HDAC/HSP90-IN-3 can suppress important virulence factors and down-regulate drug-resistant genes ERG11 and CDR1[1].

  • CAS Number: 2700035-54-5
  • MF: C26H33N5O6
  • MW: 511.57
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diprotin A TFA (Ile-Pro-Pro (TFA))

Diprotin A (TFA) is an inhibitor of dipeptidyl peptidase IV (DPP-IV).

  • CAS Number: 209248-71-5
  • MF: C19H32F3N3O6
  • MW: 455.47
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KRIBB11

KRIBB11 is an inhibitor of Heat shock factor 1 (HSF1), with IC50 of 1.2 μM.

  • CAS Number: 342639-96-7
  • MF: C13H12N6O2
  • MW: 284.273
  • Catalog: HSP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 535.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 277.3±30.1 °C

PF-3845

PF-3845 is a selective fatty acid amide hydrolase (FAAH) inhibitor (Ki = 0.23 μM); showing negligible activity against FAAH2.IC50 value: 0.23 uMTarget: FAAHPF-3845 selectively inhibits FAAH by carbamylating FAAH's serine nucleophile [1]. PF-3845 treated mice (10 mg/kg, i.p.) shows rapid and complete inactivation of FAAH in the brain, as judged by competitive activity-based protein profiling (ABPP) with the serine hydrolase-directed probe fluorophosphonate (FP)-rhodamine. PF-3845 shows a long duration of action up to 24 hour. PF-3845-treated mice also shows dramatic (>10-fold) elevation in brain levels of AEA and other NAEs (N-pamitoyl ethanolamine [PEA] and N-oleoyl ethanolamine [OEA]). FAAH is AEA-degrading enzyme fatty acid amide hydrolase. PF-3845 (1–30 mg/kg, oral administration [p.o.]) causes a dose dependent inhibition of mechanical allodynia with a minimum effective dose (MED) of 3 mg/kg (rats are analyzed at 4 hour post dosing with PF-3845). At higher doses (10 and 30 mg/kg), PF-3845 inhibits pain responses to an equivalent, if not greater, degree than the nonsteroidal anti-inflammatory drug naproxen (10mg/kg, p.o.) [1]. PF-3845 (10 mg/kg, i.p.) significantly reverses LPS-induced tactile allodynia, but doesn't modify paw withdrawal thresholds in the saline-injected paw [2].

  • CAS Number: 1196109-52-0
  • MF: C24H23F3N4O2
  • MW: 456.460
  • Catalog: FAAH
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 623.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.9±31.5 °C

Mutant IDH1-IN-1

Mutant IDH1-IN-1 is a mutant-selective IDH1 inhibitor with with IC50s of 4, 42, 80 and 143 nM against mutant IDH1 R132C/R132C, IDH1 R132H/R132H, IDH1 R132H/WT and wild type IDH1, respectively.

  • CAS Number: 1355326-21-4
  • MF: C30H31FN4O2
  • MW: 498.591
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aeruginosin 98-B

Aeruginosin 98-B is a protease inhibitor. Aeruginosin 98-B inhibits trypsin, plasmin and thrombin with IC50 values of 0.6, 7.0 and 10.0 μg/mL, respectively[1].

  • CAS Number: 167228-01-5
  • MF: C29H46N6O9S
  • MW: 654.77500
  • Catalog: Protease-Activated Receptor (PAR)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A