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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WYC-209

WYC-209, a synthetic retinoid, inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs) with an IC50 of 0.19 μM, has long-term effects and little toxicity, and induces TRCs apoptosis primarily via the caspase 3 pathway. The primary cellular target of WYC-209 is retinoic acid receptor (RAR)[1].

  • CAS Number: 2131803-90-0
  • MF: C20H20N2O3S
  • MW: 368.45
  • Catalog: RAR/RXR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bergamotine

Bergamottin is a potent and competitive CYP1A1 inhibitor with a Ki of 10.703 nM.

  • CAS Number: 7380-40-7
  • MF: C21H22O4
  • MW: 338.397
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 503.7±50.0 °C at 760 mmHg
  • Melting Point: 75-80ºC
  • Flash Point: 258.4±30.1 °C

Moveltipril

Moveltipril is a potent angiotensin converting enzyme (ACE) inhibitor[1].

  • CAS Number: 85856-54-8
  • MF: C19H30N2O5S
  • MW: 398.51700
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: 1.248g/cm3
  • Boiling Point: 658.9ºC at 760 mmHg
  • Melting Point: 113-116°
  • Flash Point: 352.3ºC

PSI-6130

PSI-6130 is a potent and selective inhibitor of HCV NS5B polymerase, and inhibits HCV replication with a mean IC50 of 0.6 μM. 

  • CAS Number: 817204-33-4
  • MF: C10H14FN3O4
  • MW: 259.234
  • Catalog: HCV
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 482.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.5±31.5 °C

1H-Tetrazole-5-carboxamide, N-(5-(3-(4-acetyl-3-hydroxy-2-propylphenox y)propoxy)-4-chloro-2-methylphenyl)-, monosodium salt

CGP-35949 sodium is a LTD4 antagonist with phospholipase inhibitory activity. CGP-35949 sodium can be used for research of asthma[1].

  • CAS Number: 111130-13-3
  • MF: C23H25ClN5NaO5
  • MW: 509.92
  • Catalog: Leukotriene Receptor
  • Density: N/A
  • Boiling Point: 597.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315ºC

PROTAC SHP2 degrader-1

PROTAC SHP2 degrader-1 is a potent and effective SHP2 degrader. PROTAC SHP2 degrader-1 induces SHP2 degradation requires binding to VHL-1 and SHP2 proteins and is also neddylation- and proteasome-dependent[1].

  • CAS Number: 2458219-65-1
  • MF: C56H79ClN12O6S2
  • MW: 1115.89
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bexarotene-d3

Bexarotene-d3 (LGD1069-d3) is the deuterium labeled Bexarotene. Bexarotene (LGD1069) is a high-affinity and selective retinoid X receptors (RXR) agonist with EC50s of 33, 24, 25 nM for RXRα, RXRβ, and RXRγ, respectively. Bexarotene shows limited affinity for RAR receptors (EC50 >10000 nM). Bexarotene can be used for the research of cutaneous T-cell lymphoma[1][2][3][4].

  • CAS Number: 166175-35-5
  • MF: C24H25D3O2
  • MW: 351.50
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mirodenafil (dihydrochloride)

Mirodenafil 2Hcl(SK3530 2Hcl) is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction.Target: PDE5Mirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor. Mirodenafil, in doses of 50 or 100 mg, significantly improved erectile function and were well tolerated in a representative population of Korean men with broad-spectrum ED of various etiologies and severities [1]. The concurrent administration of mirodenafil with alcohol was not associated with clinically significant hemodynamic changes in these healthy male volunteers in Korea. The pharmacoki-netics of mirodenafil were not significantly altered by this concurrent administration. Mirodenafil administered with alcohol had a tolerability profile comparable to that of mirodenafil alone [2]. In these healthy Korean male volunteers, the coadministration of ketoconazole and rifampicin resulted in significant changes in systemic exposure to mirodenafil [3].

  • CAS Number: 862189-96-6
  • MF: C26H39Cl2N5O5S
  • MW: 604.58900
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganetespib(STA-9090)

Ganetespib is a heat shock protein 90 (HSP90) inhibitor which exhibits potent cytotoxicity in a wide variety of hematological and solid tumor cell lines.

  • CAS Number: 888216-25-9
  • MF: C20H20N4O3
  • MW: 364.398
  • Catalog: HSP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 685.8±57.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.5±32.1 °C

AFP464

AFP464, is an active HIF-1α inhibitor with an IC50 of 0.25 μM, also is a potent aryl hydrocarbon receptor (AhR) activator.

  • CAS Number: 468719-52-0
  • MF: C22H23F3N4O3
  • MW: 448.44
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Patamostat

Patamostat (E-3123) is a potent protease inhibitor. Patamostat potently inhibits trypsin, plasmin and thrombin with IC50s of 39 nM, 950 nM and 1.9 μM, respectively. E-3123 may possess suppressing effects on pathogenesis and development of acute pancreatitis[1][2].

  • CAS Number: 114568-26-2
  • MF: C20H20N4O4S
  • MW: 412.46200
  • Catalog: Ser/Thr Protease
  • Density: 1.41g/cm3
  • Boiling Point: 701.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 378.1ºC

Patulitrin

Patulitrin has scavenging effect in the DPPH radical. Patulitrin inhibits soybean lipoxygenase. Patulitrin also has antihypertensive effect. Patulitrin is an antioxidant flavonoid that can be isolated from Anthemis tinctoria[1][2].

  • CAS Number: 19833-25-1
  • MF: C22H22O13
  • MW: 494.40
  • Catalog: 5-Lipoxygenase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Isobutyl-1-methylxanthine

IBMX is a broad-spectrum phosphodiesterase (PDE) inhibitor, with IC50s of 6.5, 26.3 and 31.7 μM for PDE3, PDE4 and PDE5, respectively.

  • CAS Number: 28822-58-4
  • MF: C10H14N4O2
  • MW: 222.244
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 445.6±37.0 °C at 760 mmHg
  • Melting Point: 200-201 °C(lit.)
  • Flash Point: 223.3±26.5 °C

RTS-V5

RTS-V5 is a dual HDAC/proteasome inhibitor with IC50s of 6.9, 18, 15, 0.27, 0.53 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, respectively.

  • CAS Number: 2285346-31-6
  • MF: C27H35N5O6
  • MW: 525.60
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP 80633

Atizoram (CP-80,633), a cyclic nucleotide phosphodiesterase (PDE4) inhibitor, elevates plasma cyclic AMP levels and decreases tumor necrosis factor-α (TNFα) production in mice[1].

  • CAS Number: 135637-46-6
  • MF: C18H24N2O3
  • MW: 316.395
  • Catalog: Phosphodiesterase (PDE)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 543.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 282.2±30.1 °C

Thymolphthalein monophosphate disodium hydrate

Thymolphthalein monophosphate disodium hydrate is a chromogenic substrate for the determination of acid phosphatase and alkaline phosphatase. Thymolphthalein is released during the reaction, increases the pH of the medium for easy detection, produces color and stops hydrolysis. Thymolphthalein monophosphate disodium hydrate can be used for the specific detection of prostatic phosphatase in serum[1][2].

  • CAS Number: 123359-43-3
  • MF: C28H31Na2O8P
  • MW: 572.49400
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: 683.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 367.1ºC

N-Nornuciferine

N-Nornuciferine is an aporphine alkaloid in lotus leaf that significantly inhibits CYP2D6 with IC50 and Ki of 3.76 and 2.34 μM, respectively.

  • CAS Number: 4846-19-9
  • MF: C18H19NO2
  • MW: 281.349
  • Catalog: Cytochrome P450
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 446.4±45.0 °C at 760 mmHg
  • Melting Point: 128-129 ºC
  • Flash Point: 182.8±18.2 °C

PROTAC CYP1B1 degrader-1

PROTAC CYP1B1 degrader-1 (Compound 6C), a α-naphthoflavone chimera derivative, is able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation, with IC50s of 95.1 and 9838.6 nM for CYP1B1 and CYP1A2, respectively. PROTAC CYP1B1 degrader-1 can be used for the research of CYP1B1-overexpressing prostate cancer[1].

  • CAS Number: 2411389-67-6
  • MF: C43H39N5O10
  • MW: 785.80
  • Catalog: Cytochrome P450
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2183240

LY2183240 is a novel and highly potent blocker of anandamide uptake (IC50 = 270 pM). LY2183240 inhibits fatty acid amide hydrolase (FAAH) activity (IC50 = 12.4 nM). IC50: 270 pM (anandamide uptake); 12.4 nM (FAAH)Target: FAAH; Anandamide uptakeFollowing i.p. administration in rats, LY2183240 increases brain anandamide concentration and exerts antinociceptive effects in formalin model of pain.

  • CAS Number: 874902-19-9
  • MF: C17H17N5O
  • MW: 307.350
  • Catalog: FAAH
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 506.1±53.0 °C at 760 mmHg
  • Melting Point: 87-88ºC
  • Flash Point: 259.9±30.9 °C

PTP inhibitor 1

PTP inhibitor 1 is a protein tyrosine phosphatase (PTP) inhibitor, with anti-angiogenic effect[1].

  • CAS Number: 2632-13-5
  • MF: C9H9BrO2
  • MW: 229.071
  • Catalog: Phosphatase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 306.7±17.0 °C at 760 mmHg
  • Melting Point: 69-71 °C(lit.)
  • Flash Point: 139.3±20.9 °C

Tolcapone

Tolcapone(Ro 40-7592) is an orally active selective, potent catechol-O-methyltransferase (COMT) inhibitor. IC50 value:Target: COMTTolcapone inhibits both central and peripheral COMT. Tolcapone caused a rapid and reversible inhibition of COMT activity in erythrocytes in parallel with a dose-dependent decrease in the formation of 3-OMD. Tolcapone increased the area under the concentration-time curve and elimination half-life of levodopa. Tolcapone crosses the blood-brain barrier, and has been used for L-DOPA adjunct therapy in the treatment of Parkinson's disease.

  • CAS Number: 134308-13-7
  • MF: C14H11NO5
  • MW: 273.241
  • Catalog: COMT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 485.6±45.0 °C at 760 mmHg
  • Melting Point: 126-128ºC
  • Flash Point: 205.7±17.2 °C

PCSK9-IN-13

PCSK9-IN-13(compound 3f) is a potent PCSK9 inhibitor, which can antagonize low-density lipoprotein (LDL) receptor binding by binding to PCSK9, with an IC50 of 537 nM[1].

  • CAS Number: 2244129-23-3
  • MF: C30H33N5O2
  • MW: 495.62
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Betrixaban hydrochloride

Betrixaban (PRT054021) hydrochloride is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with an IC50 of 1.5 nM. Betrixaban hydrochloride shows antithrombotic effect[1][3].

  • CAS Number: 2099719-47-6
  • MF: C23H23Cl2N5O3
  • MW: 488.37
  • Catalog: Factor Xa
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cbl-b-IN-13

Cbl-b-IN-13 (Example 520) is a Cbl-b inhibitor with an IC50 of <100 nM. Cbl-b-IN-13 has the ability to activate T-cells[1].

  • CAS Number: 2368841-85-2
  • MF: C29H30F3N5O2
  • MW: 537.58
  • Catalog: E1/E2/E3 Enzyme
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RXPA 380

RXPA 380 is a C-terminal specific angiotensin-converting enzyme (ACE) inhibitor with a Ki of 3 nM. RXPA 380 inhibits C-domain mutants of human recombinant ACE with an IC50 of 2.5 nM[1].

  • CAS Number: 564479-79-4
  • MF: C33H36N3O7P
  • MW: 617.63
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Perindopril-d4 erbumine

Perindopril-d4 t-butylamine salt is the deuterium labeled Perindopril t-butylamine salt. Perindopril t-butylamine salt is a long-acting ACE inhibitor of which is used to treat high blood pressure, heart failure or stable coronary artery disease[1][2].

  • CAS Number: 1356929-59-3
  • MF: C23H39D4N3O5
  • MW: 445.62900
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-Lys-Trp-OH acetate salt

H-Lys-Trp-OH (KW) is an ACE inhibitory peptide with an IC50 of 7.8 μM[1].

  • CAS Number: 50674-18-5
  • MF: C17H24N4O3
  • MW: 332.40
  • Catalog: Angiotensin-converting Enzyme (ACE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ND-336

A selective inhibitor of the gelatinases MMP2 and MMP9 and MMP13 with Ki of 85, 150 and 120 nM, respectively; has minimal effect on other MMPs; accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition.

  • CAS Number: 1807453-83-3
  • MF: C16H17NO3S2•HCl
  • MW: 371.902
  • Catalog: MMP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isovalerylcarnitine-d9 chloride

Isovalerylcarnitine-d9 (chloride) is the deuterium labeled Isovalerylcarnitine (chloride)[1]. Isovalerylcarnitine chloride, a product of the catabolism of L-leucine, is a potent activator of the Ca2+-dependent proteinase (calpain) of human neutrophils[2].

  • CAS Number: 1334532-23-8
  • MF: C12H15D9ClNO4
  • MW: 290.83
  • Catalog: Proteasome
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AC-SER-GLN-ASN-TYR-PRO-VAL-VAL-NH2

Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 is a substrato peptídico of HIV-1 protease.Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 acts as the variable substrate in a peptidolytic assay to quantify the inhibition of the protease[1][2].

  • CAS Number: 121822-32-0
  • MF: C38H58N10O12
  • MW: 846.92700
  • Catalog: HIV Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A