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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lipoic acid

Lipoic acid ((R)-(+)-α-Lipoic acid) is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes. (R)-(+)-α-Lipoic acid is more effective than racemic Lipoic acid.

  • CAS Number: 1200-22-2
  • MF: C8H14O2S2
  • MW: 206.326
  • Catalog: Mitochondrial Metabolism
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 362.5±11.0 °C at 760 mmHg
  • Melting Point: 46-49ºC
  • Flash Point: 173.0±19.3 °C

BMS-779788

BMS-779788 is a LXR partial agonist with IC50 values of 68 nM for LXRα and 14 nM for LXRβ.

  • CAS Number: 918348-67-1
  • MF: C28H29ClN2O3S
  • MW: 509.060
  • Catalog: LXR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 738.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 400.6±35.7 °C

GSK256066

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7.IC50 value: 3.2 pM [1]Target: PDE4Bin vitro: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity [1].in vivo: GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat [1]. GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats [2]. GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes [3].

  • CAS Number: 801312-28-7
  • MF: C27H26N4O5S
  • MW: 518.584
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 791.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 432.6±32.9 °C

MBCQ

MBCQ is a potent and selective cGMP-specific phosphodiesterase (PDE V; PDE5) inhibitor with an IC50 of 19 nM. MBCQ lacks inhibitory activity toward other PDE isozymes (all IC50s>100 μM). MBCQ dilates coronary arteries via specific inhibition of cGMP-PDE[1][2][3].

  • CAS Number: 150450-53-6
  • MF: C16H12ClN3O2
  • MW: 313.73800
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATX inhibitor 18

ATX inhibitor 18 is a potent ATX inhibitor with an IC50 value of 24.2 nM. ATX inhibitor 18 shows antiproliferative activity and anti-fibrosis activity. ATX inhibitor 18 suppresses collagen deposition in TGF-β-mediated cardiac fibrosis[1].

  • CAS Number: 2402772-30-7
  • MF: C21H17Cl2FN6O
  • MW: 459.30
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-S 7009

TC-S 7009 is a potent and selective HIF-2α inhibitor with a Kd of 81 nM. TC-S 7009 is more selective for HIF-2α than HIF-1α (Kd ≫ 5 μM). TC-S 7009 disrupts HIF-2α heterodimerization, decreases DNA-binding activity, and reduces HIF-2α target gene expression[1][2].

  • CAS Number: 1422955-31-4
  • MF: C12H6ClFN4O3
  • MW: 308.65200
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMG-3969

AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.

  • CAS Number: 1361224-53-4
  • MF: C21H20F6N4O3S
  • MW: 522.464
  • Catalog: Glucokinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 648.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.2±34.3 °C

Microcystin-LA

Microcystin LA, a natural toxin, exerts its cytotoxic exects by inhibiting the serine-threonine protein phosphatases PP1 and PP2A with IC50s of 0.3 and 0.3 nM, respectively[1].

  • CAS Number: 96180-79-9
  • MF: C46H67N7O12
  • MW: 910.064
  • Catalog: Phosphatase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1237.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 701.9±34.3 °C

Ganoderic Acid C6

Ganoderic acid C6 has aldose reductase inhibitory activity[1].

  • CAS Number: 105742-76-5
  • MF: C30H42O8
  • MW: 530.65
  • Catalog: Aldose Reductase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 708.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 396.1±29.4 °C

AGI-5198

AGI-5198 is a potent and selective mutant IDH1R132H inhibitor with an IC50 of 0.07 μM.

  • CAS Number: 1355326-35-0
  • MF: C27H31FN4O2
  • MW: 462.559
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 707.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.7±32.9 °C

β-FXR antagonist 1

β-FXR antagonist 1 (C 12), an isomer of FXR antagonist 1 (HY-151481) is a FXR antagonist[1].

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

IDO1-IN-19

IDO1-IN-19 (Compound 17) is a potent inhibitor of IDO1. IDO1-IN-19 has the potential for the research of cancer diseases[1].

  • CAS Number: 2328099-11-0
  • MF: C25H22F4N2O3
  • MW: 474.45
  • Catalog: Indoleamine 2,3-Dioxygenase (IDO)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PK 44 phosphate

PK44 phosphate is a potent dipeptidyl peptidase IV (DPP-IV) inhibitor with an IC50 value of 15.8 nM[1].

  • CAS Number: 1017682-66-4
  • MF: C17H16F5N7O•H3PO4
  • MW: 527.34
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gemlapodect

Gemlapodect (RO554965) is an inhibitor of phosphodiesterase 10A (PDE10A). Gemlapodect can be used for researching schizophrenia[1].

  • CAS Number: 1380329-87-2
  • MF: C22H21N7O3
  • MW: 431.45
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Obeticholic acid

INT-747 is a potent and selective farnesoid X receptor (FXR) agonist with an EC50 of 99 nM.

  • CAS Number: 459789-99-2
  • MF: C26H44O4
  • MW: 420.625
  • Catalog: FXR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 562.9±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.3±19.7 °C

SHP2-IN-6

SHP2-IN-6 is a potent SHP2 inhibitor, extracted from patent WO2017211303A1, compound 7, has an IC50 of 25.8 nM[1].

  • CAS Number: 2169223-48-5
  • MF: C22H26F2N6O2S
  • MW: 476.54
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-356278

GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1].

  • CAS Number: 720704-34-7
  • MF: C21H25N7O2S
  • MW: 439.53400
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MEDICA 16

MEDICA16, an ATP-citrate lyase inhibitor, significantly reduces intracellular TG content in gastrocnemius muscle, and this reduction is accompanied by an increase in insulin sensitivity. MEDICA16 is a selective agonist for GPR40 as well as selective partial agonists for GPR120[1][2].

  • CAS Number: 87272-20-6
  • MF: C20H38O4
  • MW: 342.513
  • Catalog: GPR120
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 485.9±18.0 °C at 760 mmHg
  • Melting Point: 154-159ºC
  • Flash Point: 261.8±17.7 °C

SM 7368

SM-7368 is a potent NF-kB inhibitor that targets downstream of MAPK p38 activation[1]. SM-7368 inhibits TNF-α-induced MMP-9 upregulation. SM-7368 can be used for the research of chemotherapies targeting TNF-α-mediated tumor invasion and metastasis [2].

  • CAS Number: 380623-76-7
  • MF: C10H5ClN4O5S
  • MW: 328.68900
  • Catalog: p38 MAPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Teneligliptin

Teneligliptin hydrobromide is a potent chemotype prolylthiazolidine-based DPP-4 inhibitor, which competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50s of approximately 1 nM.

  • CAS Number: 906093-29-6
  • MF: C22H32.5N6OSBr2.5
  • MW: 628.86
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • 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

SF1670

SF1670 is a potent and specific phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor.

  • CAS Number: 345630-40-2
  • MF: C19H17NO3
  • MW: 307.343
  • Catalog: Phosphatase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 554.1±29.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.0±24.4 °C

IDH1 Inhibitor 2

IDH1 Inhibitor 2 is a potent IDH1 inhibitor via a direct covalent modification of His315, with an IC50 of 110 nM[1].

  • CAS Number: 2244895-42-7
  • MF: C26H22N4O
  • MW: 406.48
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tetrahydropiperin

Tetrahydropiperine, a cyclohexyl analogue of piperine, is the first natural aryl pentanamide from Piper longum[1]. Tetrahydropiperine (compound 14) inhibits the cytochrome P450 (CYP) isoform CYP1A1/arylhydrocarbon hydroxylase (AHH; IC50=23 µM)[2].

  • CAS Number: 23434-88-0
  • MF: C17H23NO3
  • MW: 289.369
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 469.9±24.0 °C at 760 mmHg
  • Melting Point: 41ºC
  • Flash Point: 238.0±22.9 °C

SEW84

SEW84 (SEW04784) is a first-in-class, specific inhibitor of the Aha1-stimulated Hsp90 (ASH) ATPase activity (IC50=0.3 uM) without inhibiting basal Hsp90 ATPase;SEW84 binds to the C-terminal domain of Aha1 (Kd=1.7 uM) to weaken its asymmetric binding to Hsp90.SEW84 inhibited the GR- and AR-dependent luciferase expression with IC50 of 1.3 uM and 0.7 uM respectively.SEW84 blocks Aha1-dependent Hsp90 chaperoning activities, including the in vitro and in vivo refolding of firefly luciferase, and the transcriptional activity of the androgen receptor in cell-based models of prostate cancer.SEW84 promotes the clearance of phosphorylated tau in cellular and tissue models of neurodegenerative tauopathy.

  • CAS Number: 259089-67-3
  • MF: C19H14F4N4Os
  • MW: 422.402
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vorasidenib (AG-881)

Vorasidenib is a pan isocitrate dehydrogenase (IDH) inhibitor.

  • CAS Number: 1644545-52-7
  • MF: C14H13ClF6N6
  • MW: 414.74
  • Catalog: Isocitrate Dehydrogenase (IDH)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

5-Phenyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide

PTP1B-IN-1 is a potent protein tyrosine phosphatase-1B (PTP1B) inhibitor with IC50 of 1.6 mM; 1,2,5-thiadiazolidin-3-one-1,1-dioxide scaffold for derivatives synthesis.

  • CAS Number: 612530-44-6
  • MF: C8H8N2O3S
  • MW: 212.22600
  • Catalog: Phosphatase
  • Density: 1.483
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A