Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Autophagy plays a wide variety of physiological and pathophysiological roles. Different selective forms of autophagy have been identified and characterized, leading to the specific degradation of organelles or pathogens. These selective pathways include the autophagic degradation of mitochondria (mitophagy), peroxisomes (pexophagy), endoplasmic reticulum (reticulophagy or ER-phagy), ribosomes (ribophagy), protein aggregates (aggrephagy), lipid droplets (lipophagy), spermatozoon-inherited organelles following fertilization (allophagy), secretory granules within pancreatic cells (zymophagy), or intracellular pathogens (xenophagy).

Autophagy consists of several sequential steps--sequestration, transport to lysosomes, degradation, and utilization of degradation products--and each step may exert different function. Autophagy signal transduction are mainly regulated by autophagy-related genes/proteins, Atgs. ATGs have unveiled much of the machinery of autophagosome formation. Furthermore, different non-ATG proteins are involved in the regulation and process of autophagy, e.g., mTOR, AMPK, AKT, AMBRA1, BCL2, DFCP1, or VPS34.

Autophagy and its dysregulation have been implicated in different human diseases or processes, such as cancer, neurodegeneration, immunity, or aging. Plenty of drugs and natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways. Small molecules that can regulate autophagy seem to have great potential to modulate the clinical course of neurodegenerative diseases or promote chemotherapeutic response in tumor models. Besides, several clinical drugs and compounds in diabetes are also found to involve regulation of autophagy.

References:
[1] Glick D, et al. J Pathol. 2010 May;221(1):3-12.
[2] Mizushima N. Genes Dev. 2007 Nov 15;21(22):2861-73.
[3] Wesselborg S, et al. Cell Mol Life Sci. 2015 Dec;72(24):4721-57.
[4] Zhang XW, et al. J Asian Nat Prod Res. 2017 Apr;19(4):314-319.


Anti-infection >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Cell Cycle/DNA Damage >
Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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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
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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Protein Tyrosine Kinase/RTK >
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Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
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Vitamin D Related >
VD/VDR
Others >
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Paroxetine hydrochloride hydrate

Paroxetine hydrochloride hemihydrate is a potent selective serotonin-reuptake inhibitor, commonly prescribed as an antidepressant and has GRK2 inhibitory ability with IC50 of 14 μM.

  • CAS Number: 110429-35-1
  • MF: C19H22ClFNO3.5
  • MW: 374.83
  • Catalog: Autophagy
  • Density: 1.213g/cm3
  • Boiling Point: 451.7ºC at 760mmHg
  • Melting Point: 121-131ºC
  • Flash Point: 227ºC

Rosuvastatin D3

Rosuvastatin D3 (ZD 4522 D3) is a deuterium labeled Rosuvastatin. Rosuvastatin (ZD 4522) is a competitive HMG-CoA reductase inhibitor with an IC50 of 11 nM[1]. Rosuvastatin potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM, delayed cardiac repolarization, and thereby prolonged action potential durations (APDs) and corrected QT interval (QTc) intervals[2].

  • CAS Number: 1133429-16-9
  • MF: C22H25D3FN3O6S
  • MW: 484.56
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Scriptaid

Scriptaid is a potent histone deacetylase (HDAC) inhibitor, used in cancer research.

  • CAS Number: 287383-59-9
  • MF: C18H18N2O4
  • MW: 326.346
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 160-161℃
  • Flash Point: N/A

Itraconazole-d5

Itraconazole-d5 (R51211-d5) is the deuterium labeled Itraconazole. Itraconazole (R51211) is a triazole antifungal agent and a potent and orally active Hedgehog (Hh) signaling pathway antagonist with an IC50 of ~800 nM. Itraconazole potently inhibits lanosterol 14α-demethylase (cytochrome P450 enzyme), thereby inhibits the oxidative conversion of lanosterol to ergosterol. Itraconazole has anticancer and antiangiogenic effects[1][2][3].

  • CAS Number: 1217510-38-7
  • MF: C35H33Cl2D5N8O4
  • MW: 710.66400
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC1999

UNC1999 is a SAM-competitive, potent and selective inhibitor of EZH1/2 with IC50s of 10 nM and 45 nM, repectively.

  • CAS Number: 1431612-23-5
  • MF: C33H43N7O2
  • MW: 569.740
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 804.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 440.4±34.3 °C

Sirtinol

Sirtinol is a sirtuin inhibitor, with IC50s of 48 μM, 57.7 μM and 131 μM for ySir2, hSIRT2 and hSIRT2, respectively.

  • CAS Number: 410536-97-9
  • MF: C26H22N2O2
  • MW: 394.465
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 659.2±50.0 °C at 760 mmHg
  • Melting Point: 119-120℃
  • Flash Point: 352.5±30.1 °C

glycycoumarin

Glycycoumarin is a major bioactive coumarin of licorice. Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress-mediated JNK and GSK-3-mediated mitochondrial pathway. Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase [1] [2].

  • CAS Number: 94805-82-0
  • MF: C21H20O6
  • MW: 368.380
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 646.9±55.0 °C at 760 mmHg
  • Melting Point: 243.5-244.5℃
  • Flash Point: 232.0±25.0 °C

Bigelovin

Bigelovin, a sesquiterpene lactone isolated from Inula helianthus-aquatica, is a selective retinoid X receptor α agonist. Bigelovin suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation[1].

  • CAS Number: 3668-14-2
  • MF: C17H20O5
  • MW: 304.33800
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fulvestrant

Fulvestrant is a potent Estrogen Receptor antagonist with an IC50 of 9.4 nM.

  • CAS Number: 129453-61-8
  • MF: C32H47F5O3S
  • MW: 606.771
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 674.8±55.0 °C at 760 mmHg
  • Melting Point: 104-106°C
  • Flash Point: 361.9±31.5 °C

Isodunnianol

Isodunnianol is a autophagy inducer. Isodunnianol induces autophagy and increases he expression of pAMPK172, pULK1555,decreases teh expression of pULK1757, SQSTM2. Isodunnianol decreases Doxorubicin (HY-15142A)-induced cardiotoxicity[1].

  • CAS Number: 139726-30-0
  • MF: C27H26O3
  • MW: 398.493
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 511.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.0±30.1 °C

Sildenafil

Sildenafil is a potent phosphodiesterase type 5 (PDE5) inhibitor with IC50 of 5.22 nM.

  • CAS Number: 139755-83-2
  • MF: C22H30N6O4S
  • MW: 474.576
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 672.4ºC at 760 mmHg
  • Melting Point: 187-189°C
  • Flash Point: 360.5ºC

Tubastatin A

Tubastatin A (TSA) TFA is a potent and selective?HDAC6?inhibitor with?IC50?of 15 nM in a cell-free assay, and is selective (1000-fold more) against all other isozymes except HDAC8 (57-fold more). Tubastatin A TFA also inhibits HDAC10 and metallo-β-lactamase domain-containing protein?2 (MBLAC2).

  • CAS Number: 1239262-52-2
  • MF: C22H22F3N3O4
  • MW: 449.42
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Crizotinib (PF-02341066)

Crizotinib is a potent inhibitor of c-Met and ALK with an IC50 of 11 nM and 24 nM in cell-based assays, respectively.

  • CAS Number: 877399-52-5
  • MF: C21H22Cl2FN5O
  • MW: 450.337
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 599.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 316.2±30.1 °C

Pemetrexed disodium

Pemetrexed is a novel antifolate, the Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively.

  • CAS Number: 137281-23-3
  • MF: C20H21N5O6
  • MW: 427.411
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALLO-1

ALLO-1, an autophagy receptor, is essential for autophagosome formation around paternal organelles and directly binds to the worm LC3 homologue LGG-1 through its LC3-interacting region (LIR) motif[1].

  • CAS Number: 37468-32-9
  • MF: C17H15ClN2O2
  • MW: 314.77
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CZC-25146-d3

CZC-25146 Hcl is a potent, selective and metabolically stable LRRK2 inhibitor with IC50 of 4.76 nM/6.87 nM for wild type LRRK2 and G2019S LRRK2 respectively.IC50 value: 4.76 nM/6.87 nM(wild type/G2019S LRRK2) [1]Target: LRRK2 CZC-25146displayed a very clean profile, it inhibited only five kinases(PLK4, GAK, TNK1, CAMKK2 and PIP4K2C) with high potency, none of which have been classified as predictors of genotoxicity or hematopoietic toxicity. CZC-25146 neither caused cytotoxicity in human cortical neurons at concentrations below 5μM over a seven-day treatment in culture nor did it block neuronal development in vitro. CZC-25146 possesses favorable pharmacokinetic properties, such as a volume of distribution of 5.4 L/kg and a clearance of 2.3 L/hr/kg that render it suitable for in-vivo studies.

  • CAS Number: 1330003-04-7
  • MF: C22H26ClFN6O4S
  • MW: 525.00
  • Catalog: LRRK2
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 697.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 375.5±34.3 °C

Dimethyl Fumarate-2,3-d2

Dimethyl fumarate-d2 is the deuterium labeled Dimethyl fumarate[1]. Dimethyl fumarate (DMF) is an orally active and brain-penetrant Nrf2 activator and induces upregulation of antioxidant gene expression. Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway, and also induces cell autophagy. Dimethyl fumarate can be used for multiple sclerosis research[2][3].

  • CAS Number: 23057-98-9
  • MF: C6H6D2O4
  • MW: 146.138
  • Catalog: HIV
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 193.0±0.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 91.1±0.0 °C

Cilengitide TFA

Cilengitide is a potent and selective integrin inhibitor for αvβ3 and αvβ5 receptor, with IC50 values of 4 nM and 79 nM, respectively.

  • CAS Number: 199807-35-7
  • MF: C29H41F3N8O9
  • MW: 702.67900
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carbamazepine-d8

Carbamazepine-d8 is the deuterium labeled Carbamazepine. Carbamazepine, a sodium channel blocker, is an anticonvulsant drug, with an IC50 of 131 μM[1][2].

  • CAS Number: 1538624-35-9
  • MF: C15H4D8N2O
  • MW: 244.32
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Microcolin H

Microcolin H is a marine lipopeptide and phosphatidylinositol transfer protein ligand that targets PITPα/β. Microcolin H increases the conversion of LC3I to LC3II and reduces p62 levels in cancer cells, leading to autophagy cell death (Autophagy). Microcolin H effectively inhibits tumor development and has anti-proliferative activity in nude mouse subcutaneous tumor models[1].

  • CAS Number: 2408008-21-7
  • MF: C38H63N5O9
  • MW: 733.93
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acadesine (AICAR)

AICAR is a cell-permeable AMP-activated protein kinase (AMPK) activator.

  • CAS Number: 2627-69-2
  • MF: C9H14N4O5
  • MW: 258.231
  • Catalog: Autophagy
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 726.3±60.0 °C at 760 mmHg
  • Melting Point: 214-215 °C
  • Flash Point: 393.1±32.9 °C

Bexarotene

Bexarotene is a selective retinoid X receptors (RXR) agonist for the treatment of cutaneous T-cell lymphoma.

  • CAS Number: 153559-49-0
  • MF: C24H28O2
  • MW: 348.478
  • Catalog: Autophagy
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 489.7±44.0 °C at 760 mmHg
  • Melting Point: 230-231ºC
  • Flash Point: 229.5±23.1 °C

Lucanthone hydrochloride

Lucanthone hydrochloride is an endonuclease inhibitor of Apurinic endonuclease-1 (APE-1).

  • CAS Number: 548-57-2
  • MF: C20H25ClN2OS
  • MW: 376.94
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 512.4ºC at 760 mmHg
  • Melting Point: 195-196ºC
  • Flash Point: 263.7ºC

APR-246

PRIMA-1MET restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

  • CAS Number: 5291-32-7
  • MF: C10H17NO3
  • MW: 199.247
  • Catalog: MDM-2/p53
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 313.8±17.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 143.6±20.9 °C

LRRK2/NUAK1/TYK2-IN-1

LRRK2/NUAK1/TYK2-IN-1 (conpound 226) shows inhibitory activity toward LRRK2 (Wt), LRRK2 (G2019), TYK2 and NUAK1, with IC50 values lower than 10 nM. LRRK2/NUAK1/TYK2-IN-1 can be used for autoimmune disease research[1].

  • CAS Number: 2629192-96-5
  • MF: C20H11F3N6
  • MW: 392.34
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brivanib Alaninate (BMS-582664)

Brivanib alaninate is an ATP-competitive inhibitor against VEGFR2 with an IC50 of 25 nM; has moderate potency against VEGFR-1 and FGFR-1, but more than 240-fold against PDGFRβ.

  • CAS Number: 649735-63-7
  • MF: C22H24FN5O4
  • MW: 441.456
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PHA-848125

Milciclib (PHA-848125) is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively.

  • CAS Number: 802539-81-7
  • MF: C25H32N8O
  • MW: 460.575
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tempol

Tempol is a general superoxide dismutase (SOD)-mimetic drug that efficiently neutralizes reactive oxygen species (ROS).

  • CAS Number: 2226-96-2
  • MF: C9H18NO2*
  • MW: 172.24
  • Catalog: Autophagy
  • Density: 1.187 g/cm3
  • Boiling Point: 269ºC
  • Melting Point: 69-71 °C(lit.)
  • Flash Point: N/A

Tigecycline

Tigecycline is a first-in-class, broad spectrum antibiotic with activity against antibiotic-resistant organisms.Target: AntibacterialTigecycline is active against a broad range of gram-negative and gram-positive bacterial species including clinically important multidrug-resistant nosocomial and community-acquired bacterial pathogens. Tigecycline has been shown to inhibit the translation elongation step by binding to the ribosome 30S subunit and preventing aminoacylated tRNAs to accommodate in the ribosomal A site [1]. Tigecycline has also been found to be effective for the treatment of community- as well as hospital-acquired and ventilator-associated pneumonia and bacteremia, sepsis with shock and urinary tract infections. Tigecycline appears to be a valuable treatment option for the management of superbugs, especially where conventional therapy has failed [2].Fifteen patients received tigecycline for 16 episodes of CPKP infection. The main infections were pneumonia (31%), urinary tract infection (31%), peritonitis (20%), catheter-related bacteraemia (12%), and meningitis (6%). Most infections were complicated with severe sepsis (44%), septic shock (12%), and/or bacteraemia (19%). The daily maintenance dose of tigecycline was 200 mg in 10 episodes and 100 mg in 6 episodes. The overall 30-day mortality rate was 25%. Univariate analysis showed that mortality was significantly associated (p < 0.01) with mean APACHE II and SOFA scores and the presence of immunosuppression, but not with the tigecycline dose [3].

  • CAS Number: 220620-09-7
  • MF: C29H39N5O8
  • MW: 585.649
  • Catalog: Bacterial
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 890.9±65.0 °C at 760 mmHg
  • Melting Point: 164-166°C
  • Flash Point: 492.6±34.3 °C

rac-Sitagliptin-d4 hydrochloride

(Rac)-Sitagliptin-d4((Rac)-MK-0431-d4) hydrochloride is a labelled racemic Sitagliptin. Sitagliptin (MK-0431) hydrochloride is a potent inhibitor of DPP4 with an IC50 of 19 nM in Caco-2 cell extracts[1].

  • CAS Number: 1620233-77-3
  • MF: C16H12D4ClF6N5O
  • MW: 411.34
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A