2. Signaling Pathways
  3. Autophagy
  4. Autophagy

Autophagy

Autophagy

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Autophagy is a conserved cellular degradation and recycling process in the lysosome. In mammalian cells, there are three primary types of autophagy: microautophagy, macroautophagy, and chaperone-mediated autophagy (CMA). Microphagy captures cargoes by means of invaginations or protrusions of the lysosomal membrane directly, CMA uses chaperones to identify cargo proteins and then unfolds and transfers them into the lysosomal, while macroautophagy sequesters cargo by autophagosomes-de novo synthesized of double-membrane vesicles-and subsequently transport it to the lysosome.

Macroautophagy is the best studied and it occurs at a low level constitutively and can also be further induced under stress conditions, such as nutrient or energy starvation with a salient feature of autophagy protein degradation. Stress-induced macrophagy plays an important role in protein catabolism with another key protein degradation pathway, the ubiquitin–proteasome system (UPS).

As the study progressed, autophagy gains its importance under basal, nutrient-rich conditions, and is now recognized as a critical housekeeping pathway in catabolism of diverse cellular constituents, such as protein aggregates (aggrephagy), lipid droplets (lipophagy), iron complex (Ferritinophagy) and carbohydrate. Except for macromolecules, autophagy can also target several organelles and structures, such as mitochondria (mitophagy), peroxisome (pexophagy), endoplasmic reticulum (reticulophagy or ER-phagy), ribosome (ribophagy), spermatozoon-inherited organelles following fertilization (allophagy), secretory granules within pancreatic cells (zymophagy) and intracellular pathogens (xenophagy).

Autophagy and its dysfunction are associated with a variety of human pathologies, including ageing, cancer, neurodegenerative disease, heart disease and metabolic diseases, such as diabetes. Plenty of drugs and natural products are involved in autophagy modulation through multiple signaling pathways. Small molecules that can regulate autophagy seem to have great potential to intervene such diseases in animal models or clinical courses.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-B1140S
    Diazoxide-d3
    		Inducer
    Diazoxide-d3 is deuterium labeled Diazoxide. Diazoxide (Sch-6783) is an ATP-sensitive potassium channel activator, has the potential for hyperinsulinism treatment.
    Diazoxide-d<sub>3</sub>
  • HY-161189
    Thalidomide-2,6-diazaspiro[3.4]octane-C-piperidine-C2-O-C-boc
    		Inducer
    Thalidomide-2,6-diazaspiro[3.4]octane-C-piperidine-C2-O-C-boc is a conjugate of E3 ligase ligand and linker, consisting of Thalidomide (HY-14658) and the corresponding Linker. Thalidomide-2,6-diazaspiro[3.4]octane-C-piperidine-C2-O-C-boc can serve as Cereblon ligand to recruit CRBN protein and serve as a key intermediate for the synthesis of complete PROTAC molecules.
    Thalidomide-2,6-diazaspiro[3.4]octane-C-piperidine-C2-O-C-boc
  • HY-A0016S
    Dronedarone-d6 hydrochloride
    		Inducer
    Dronedarone-d6 (hydrochloride) is the deuterium labeled Dronedarone. Dronedarone hydrochloride, a derivative of Amiodarone (HY-14187), is a class III antiarrhythmic agent for the study of atrial fibrillation (AF) and atrial flutter. Dronedarone hydrochloride is a potent blocker of multiple ion currents, including potassium current, sodium current, and L-type calcium current, and exhibits antiadrenergic effects by noncompetitive binding to β-adrenergic receptors. Dronedarone hydrochloride is a substrate for and a moderate inhibitor of CYP3A4.
    Dronedarone-d<sub>6</sub> hydrochloride
  • HY-176220
    GPX4-AUTAC
    GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader (AUTAC). GPX4-AUTAC consists of an inhibitor ML162-yne (HY-153748), a degradation tag FBnG (HY-W073762) and a glycol linker (HY-W021401). GPX4-AUTAC promotes the ubiquitination of GPX4 by E3 ligase TRAF6, and enhances the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. GPX4-AUTAC significantly induces ferroptosis and shows a potent anti-cancer activity in breast cancer cells, breast cancer-derived organoids (PDOs) and MDA-MB-231 tumor xenograft mice model, with potent synergistic effects when combined with Sulfasalazine (SAS) (HY-14655) or chemotherapy drugs (Paclitaxel (HY-B0015) or Cisplatin (HY-17394)).
    GPX4-AUTAC
  • HY-100561S1
    Tempol-d17
    Tempol-d17 is the deuterium labeled Tempol. Tempol is a general superoxide dismutase (SOD)-mimetic agent that efficiently neutralizes reactive oxygen species (ROS).
    Tempol-d<sub>17</sub>
  • HY-N0893S
    Tetrahydrocurcumin-d6
    		Inducer
    Tetrahydrocurcumin-d6 is a deuterium labeled Tetrahydrocurcumin. Tetrahydrocurcumin is a Curcuminoid which displays inhibitory activity for CYP2C9 and CYP3A4.
    Tetrahydrocurcumin-d<sub>6</sub>
  • HY-B0444S1
    Maprotiline-d3 hydrochloride
    		Inducer 98.80%
    Maprotiline-d3 (hydrochloride) is deuterium labeled Maprotiline (hydrochloride).
    Maprotiline-d<sub>3</sub> hydrochloride
  • HY-14605S
    Rasagiline-13C3 mesylate
    		Inducer
    Rasagiline-13C3 ((R)-AGN1135-13C3; TVP1012-13C3) mesylate is the deuterium labeled Rasagiline (mesylate) (HY-14605). Rasagiline (R-AGN1135) mesylate is a highly potent selective irreversible mitochondrial monoamine oxidase (MAO) inhibitor with IC50s of 4.43 nM and 412 nM for rat brain MAO B and A activity, respectively.
    Rasagiline-<sup>13</sup>C<sub>3</sub> mesylate
  • HY-A0077S2
    Perphenazine-d6 fumarate
    		Inhibitor
    Perphenazine-d6 (fumarate) is a deuterated labeled Perphenazine. Perphenazine is an orally active dopamine receptor and histamine-1 receptor antagonist, with Ki values of 0.56 nM (D2), 0.43 nM (D3), 6 nM (5-HT2A), respectively. Perphenazine also binds to Alpha-1A adrenergic receptor. Perphenazine inhibits cancer cell proliferation, and induces apoptosis. Perphenazine can be used in the research of mental disease, cancer, inflammation.
    Perphenazine-d<sub>6</sub> fumarate
  • HY-162879
    FAK inhibitor 7
    		Inducer
    FAK inhibitor 7 is a type of FAK inhibitor with an IC50 value of 3.58 nM. FAK inhibitor 7 can inhibit the downstream signaling cascades of FAK (like Src and AKT), causing ovarian cancer cells to stall in the G0/G1 phase and induce cytotoxic autophagy. FAK inhibitor 7 can also suppress tumor metastasis and growth in ovarian cancer mice.
    FAK inhibitor 7
  • HY-16562AS
    Irinotecan-d5 hydrochloride
    		Inducer
    Irinotecan-d5 hydrochloride is deuterated labeled Irinotecan hydrochloride (HY-16562A). Irinotecan hydrochloride ((+)-Irinotecan hydrochloride) is a topoisomerase I inhibitor mainly used to treat colon cancer and rectal cancer.
    Irinotecan-d<sub>5</sub> hydrochloride
  • HY-A0077A
    Perphenazine dihydrochloride
    		Inhibitor
    Perphenazine dihydrochloride is an orally active dopamine receptor and histamine-1 receptor antagonist, with Ki values of 0.56 nM (D2), 0.43 nM (D3), 6 nM (5-HT2A), respectively. Perphenazine dihydrochloride also binds to Alpha-1A adrenergic receptor. Perphenazine dihydrochloride inhibits cancer cell proliferation, and induces apoptosis. Perphenazine dihydrochloride can be used in the research of mental disease, cancer, inflammation.
    Perphenazine dihydrochloride
  • HY-B1039AR
    Ambroxol hydrochloride (Standard)
    		Inducer
    Ambroxol (hydrochloride) (Standard) is the analytical standard of Ambroxol (hydrochloride). This product is intended for research and analytical applications. Ambroxol hydrochloride (NA-872 hydrochloride), an active metabolite of the proagent Bromhexine, has potent expectorant effects. Ambroxol hydrochloride is a glucocerebrosidase (GCase) chaperone and increases glucocerebrosidase activity. Ambroxol hydrochloride induces lung autophagy and has the potential for Parkinson disease and neuronopathic Gaucher disease research.
    Ambroxol hydrochloride (Standard)
  • HY-N6602R
    α-Solanine (Standard)
    		Inducer
    α-Solanine (Standard) is the analytical standard of α-Solanine. This product is intended for research and analytical applications. α-solanine, a bioactive component and one of the major steroidal glycoalkaloids in Solanum nigrum, has been observed to inhibit growth and induce apoptosis in cancer cells.
    α-Solanine (Standard)
  • HY-Y1269I
    Ammonium chloride, United States Pharmacopeia (USP) Reference Standard
    		Inhibitor
    Ammonium chloride United States Pharmacopeia (USP) Reference Standard (Salmiac, Pharmaceutical primary standard, USP) is a reagent that can be used in cell culture to provide a source of nitrogen. Ammonium chloride can be used as a heteropolar compound to regulate pH value, which can cause intracellular alkalination and metabolic acidosis, thus affecting the activity of enzymes and affecting the process of biological systems. Ammonium chloride is also a lysosome inhibitor.
    Ammonium chloride, United States Pharmacopeia (USP) Reference Standard
  • HY-147656
    NAMPT degrader-1
    		Inducer
    NAMPT degrader-1 (Compound A3), an autophagosome-tethering compound (ATTEC), is an nicotinamide phosphoribosyltransferase (NAMPT) degrader with an IC50 of 0.023 μM. NAMPT degrader-1 significantly induces the degradation of NAMPT through the autophagy-lysosomal pathway and shows excellent cellular antitumor potency.
    NAMPT degrader-1
  • HY-15296S1
    Cabergoline-d6
    		Inducer
    Cabergoline-d6 is deuterium labeled Cabergoline. Cabergoline is an ergot derived-dopamine D2-like receptor agonist that has high affinity for D2, D3, and 5-HT2B receptors (Ki=0.7, 1.5, and 1.2, respectively).
    Cabergoline-d<sub>6</sub>
  • HY-172225
    [Ru(phen)2(HMPIP)](PF6)2
    		Inducer
    [Ru(phen)2(HMPIP)](PF6)2 (Compound 6A) is an anti-tumor agent. [Ru(phen)2(HMPIP)](PF6)2 can inhibit the proliferation and migration of HepG2 liver cancer cells, and induce apoptosis, autophagy, cell cycle arrest and ferroptosis of HepG2 liver cancer cells. [Ru(phen)2(HMPIP)](PF6)2 exerts its anti-tumor activity by stimulating immune response to increase CD8+ T cells.
    [Ru(phen)2(HMPIP)](PF6)2
  • HY-B0715R
    Pentoxifylline (Standard)
    		Inducer
    Pentoxifylline (Standard) is the analytical standard of Pentoxifylline. This product is intended for research and analytical applications. Pentoxifylline (BL-191), a haemorheological agent, is an orally active non-selective phosphodiesterase (PDE) inhibitor, with immune modulation, anti-inflammatory, hemorheological, anti-fibrinolytic and anti-proliferation effects. Pentoxifylline can be used for the research of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation.
    Pentoxifylline (Standard)
  • HY-156405
    FTO-IN-10
    		Inducer
    FTO-IN-10 (compound 7) is a potent human demethylase FTO (the fat mass and obesity-associated protein) inhibitor with an IC50 of 4.5 μM. FTO-IN-10 enters the FTO’s structural domain II binding pocket through hydrophobic and hydrogen bonding interactions. FTO-IN-10 induces DNA damage and autophagic cell death in A549 cells.
    FTO-IN-10
Cat. No. Product Name / Synonyms Application Reactivity
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