The PI3K/Akt/mTOR signaling pathways is crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions. PI3Ks constitute a lipid kinase family. Class I PI3Ks are heterodimers composed of a catalytic (CAT) subunit (i.e., p110) and an adaptor/regulatory subunit (i.e., p85), and can be further divided into two subclasses: subclass IA (PI3Kα, β, and δ), which is activated by receptors with protein tyrosine kinase activity, and subclass IB (PI3Kγ), which is activated by receptors coupled with G proteins. Akt kinases belong to the AGC kinase family, related to AMP/GMP kinases and protein kinase C. mTOR is a key protein evolutionarily conserved from yeast to man and is essential for life. The mTORC1 complex is made up of mTOR, Raptor, mLST8, and PRAS40, and the mTORC2 complex is composed of mTOR, Rictor, Sin1, and mLST8.

Upon ligand binding, phosphorylated tyrosine residing in activated RTKs will bind to p85, then release the catalytic subunit p110. Activated p110 phosphorylated the PIP2 into the second messenger PIP3, and this reaction can be reversed by the PI3K antagonist PTEN. PIP3 will recruit the downstream Akt to inner membranes and phosphorylates Akt on its serine/threonine kinase sites (Thr308 and Ser473). Activated Akt is involved in the downstream mTORC1 mediated response to biogenesis of protein and ribosome.

Many genes belonging to the PI3K/Akt pathway have been implicated in the pathophysiology of solid tumors and sensitivity/resistance to chemotherapy. More and more studies are now focusing on the translational relevance of targeting these pathways in cancer therapy.

References:
[1] Porta C, et al. Front Oncol. 2014 Apr 14;4:64.
[2] Follo MY, et al. Adv Biol Regul. 2015 Jan;57:10-6.
[3] Li X, et al. Oncotarget. 2016 May 31;7(22):33440-50.


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 >
Autophagy LRRK2 ULK Mitophagy
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
Cytoskeleton >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
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GPCR/G Protein >
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JAK/STAT Signaling >
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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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Stem Cell/Wnt >
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
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Vitamin D Related >
VD/VDR
Others >
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Orobol

Orobol is one of the major soy isoflavones and has various pharmacological activities, including anti-skin-aging and anti-obesity effects. Orobol inhibits CK1ε, VEGFR2, MAP4K5, MNK1, MUSK, TOPK, and TNIK (IC50=1.24-4.45 μM). Orobol also inhibits PI3K isoforms (IC50=3.46-5.27 μM for PI3K α/β/γ/K/δ)[1][2].

  • CAS Number: 480-23-9
  • MF: C15H10O6
  • MW: 286.236
  • Catalog: Casein Kinase
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 616.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.5±25.0 °C

MMP-9-IN-4

MMP-9-IN-4 is a MMP-9 inhibitor (IC50: 7.46 nM) that has H-π interactions with MMP-9. MMP-9-IN-4 also inhibits AKT activity (IC50: 8.82 nM). MMP-9-IN-4 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-4 can be used in the research of cancers[1].

  • CAS Number: 2581824-39-5
  • MF: C28H19F3N4O6
  • MW: 564.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TGR-1202 Tosylate

Umbralisib (TGR-1202) tosylate is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC50 of 22.2 nM and 6.0 μM, respectively. Umbralisib tosylate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib tosylate can be used for haematological malignancies reseach[1][2][3][4].

  • CAS Number: 1532533-72-4
  • MF: C38H32F3N5O6S
  • MW: 743.75100
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 138 - 141 °C
  • Flash Point: N/A

VX-984

VX-984 is a potent DNA-PKinhibitor.

  • CAS Number: 1476074-39-1
  • MF: C23H21D2N7O
  • MW: 415.49
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-6

PI3K/mTOR Inhibitor-6 (Compound 19c) is a potent and dual inhibitor of PI3K/mTOR. PI3K/mTOR Inhibitor-6 displays better stability in artificial gastric fluids than gedatolisib. PI3K/mTOR Inhibitor-6 significantly suppresses the PI3K/Akt/mTOR signaling pathway at 10 μM. PI3K/mTOR Inhibitor-6 has the potential for the research of cancer diseases[1].

  • CAS Number: 2456295-59-1
  • MF: C30H34N10O4
  • MW: 598.66
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BKM120

NVP-BKM120 is a pan-class I PI3K inhibitor, with IC50s of 52, 166, 116 and 262 nM for p110α, p110β, p110δ and p110γ, respectively.

  • CAS Number: 944396-07-0
  • MF: C18H21F3N6O2
  • MW: 410.393
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 645.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.3±34.3 °C

Wortmannin

Wortmannin is a multi-target inhibitor of PI3K and MLCK with IC50s of 3 nM and 200 nM, respectively. Wortmannin is also a potent inhibitor of DNA-PK (IC50, 16 nM) and ATM (IC50, 150 nM). Wortmannin is also a potent inhibitor of Polo-like kinase (Plk).

  • CAS Number: 19545-26-7
  • MF: C23H24O8
  • MW: 428.432
  • Catalog: ATM/ATR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 615.6±55.0 °C at 760 mmHg
  • Melting Point: 234-240ºC
  • Flash Point: 326.1±31.5 °C

Temsirolimus (CCI-779)

Temsirolimus is an inhibitor of mTOR with an IC50 of 1.76 μM.

  • CAS Number: 162635-04-3
  • MF: C56H87NO16
  • MW: 1030.287
  • Catalog: mTOR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1048.4±75.0 °C at 760 mmHg
  • Melting Point: 99-101ºC
  • Flash Point: 587.8±37.1 °C

7BIO

7BIO (7-Bromoindirubin-3-Oxime) is the derivate of indirubin. 7BIO (7-Bromoindirubin-3-Oxime) has inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β). 7BIO (7-Bromoindirubin-3-Oxime) inhibits Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, activation of astrocytes and microglia, and attenuates Aβ oligomer-induced cognitive impairments in mice[1].

  • CAS Number: 916440-85-2
  • MF: C16H10BrN3O2
  • MW: 356.17400
  • Catalog: CDK
  • Density: 1.80±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 565.5±50.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

(2R)-L-gamma-Glutamyl-3-((2-((bis(bis(2-chloroethyl)amino)phosphinyl)oxy) ethyl)sulfonyl)- L-alanyl-2-phenylglycine

Canfosfamide (TLK-286, TER286) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. Canfosfamide also inhibits the catalytic kinase activity of DNA-dependent protein kinase (DNA-PK). Canfosfamide produces an anticancer alkylating agent and a glutathione derivative after activation. Canfosfamide can be used to research malignancies[1][2][3].

  • CAS Number: 158382-37-7
  • MF: C26H40Cl4N5O10PS
  • MW: 787.47400
  • Catalog: Apoptosis
  • Density: 1.484g/cm3
  • Boiling Point: 939.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 522.2ºC

oleoylglycine

N-Oleoyl glycine is a lipoamino acid, which stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte.

  • CAS Number: 2601-90-3
  • MF: C20H37NO3
  • MW: 339.513
  • Catalog: Cannabinoid Receptor
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 525.6±43.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.7±28.2 °C

GSK-3β inhibitor 13

GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].

  • CAS Number: 2227316-74-5
  • MF: C23H22N6O2
  • MW: 414.46
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

APY0201

APY0201 is a potent PIKfyve inhibitor, which inhibits the conversion of PtdIns3P to PtdIns(3,5)P2 in the presence of in the presence of [33P]ATP with an IC50 of 5.2 nM. APY0201 also inhibits IL-12/IL-23 production.

  • CAS Number: 1232221-74-7
  • MF: C23H23N7O
  • MW: 413.47500
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TGR-1202 Sulfate

Umbralisib sulfate is an orally active, potent and selective dual PI3Kδ and casein kinase-1-ε (CK1ε) inhibitor, with EC50 of 22.2 nM and 6.0 μM, respectively. Umbralisib sulfate exhibits unique immunomodulatory effects on chronic lymphocytic leukemia (CLL) T cells. Umbralisib sulfate can be used for haematological malignancies reseach[1][2][3][4].

  • CAS Number: 1532533-75-7
  • MF: C31H26F3N5O7S
  • MW: 669.62800
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 125 - 127 °C
  • Flash Point: N/A

Hirsutenone

Hirsutenone is an active botanical diarylheptanoid present in Alnus species and exhibits many biological activities, including anti-inflammatory, anti-tumor promoting and anti-atopic dermatitis effects. Hirsutenone attenuates adipogenesis by binding directly to PI3K and ERK1 in a non-ATP competitive manner. Hirsutenone can be used for the study of obesity[1].

  • CAS Number: 41137-87-5
  • MF: C19H20O5
  • MW: 328.359
  • Catalog: ERK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 622.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.0±28.0 °C

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

hSMG-1 inhibitor 11j

hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. hSMG-1 inhibitor 11j exhibits >455-fold selectivity for hSMG-1 over mTOR (IC50=50 nM), PI3Kα/γ (IC50=92/60 nM) and CDK1/CDK2 (IC50=32/7.1 μM). hSMG-1 inhibitor 11j can be used for the research of cancer[1].

  • CAS Number: 1402452-15-6
  • MF: C27H28ClN7O3S
  • MW: 566.074
  • Catalog: CDK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Apoptin-derived peptide

Apoptin-derived peptide is an antitumor polypeptide with cytotoxicity. Apoptin-derived peptide promotes apoptosis and necrosis of gastric cancer (GC) cells by regulating PI3K/AKT/ARNT signaling. Apoptin-derived peptide inhibited the invasion and migration of cancer cells, and inhibited the expression and phosphorylation of the subunit p85 of PI3K, which further inhibited the PI3K/AKT pathway involved in the development of gastric cancer[1].

  • CAS Number: 2232156-31-7
  • MF: C223H417N89O50S
  • MW: 5177.33
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lithium chloride monohydrate

Lithium chloride hydrate, an orally active mood stabilizer, is a potent virus inhibitor and effective immunomodulatory agent. Lithium chloride hydrate has antidepressant activity by inhibiting GSK3β and promoting neurogenesis. Lithium chloride hydrate alleviates cognition dysfunction and the symptoms of acute mania and depression. Lithium chloride hydrate can also be used for research of virus infection and Alzheimer's disease[1][2][3].

  • CAS Number: 85144-11-2
  • MF: ClH2LiO
  • MW: 60.40930
  • Catalog: Apoptosis
  • Density: 1.21 g/mL at 20 °C
  • Boiling Point: 1382 °C
  • Melting Point: 605 °C(lit.)
  • Flash Point: -4 °F

AICAR phosphate

AICAR phosphate is an activator of AMP-activated protein kinase (AMPK), down-regulates the insulin receptor expression in HepG2 cells.

  • CAS Number: 681006-28-0
  • MF: C9H17N4O9P
  • MW: 356.23
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Methylhemeanthidine chloride

N-Methylhemeanthidine chloride is an amaryllidaceae alkaloid isolated from Zephyranthes candida. N-Methylhemeanthidine chloride has antitumor activity and can inhibit cancer cell proliferation by down-regulating < a href=" " class="link-product" target="_blank">AKT activation, mediating cell cycle arrest and inducing < a href=" " class="link-product" target="_blank">apoptosis[1].

  • CAS Number: 1807688-81-8
  • MF: C18H22ClNO5
  • MW: 367.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KDU691

KDU691 is a PI4K inhibitor.

  • CAS Number: 1513879-19-0
  • MF: C22H18ClN5O2
  • MW: 419.864
  • Catalog: PI4K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-9

PI3K/mTOR Inhibitor-9 (Compound 1) is a potent mTOR and PI3K inhibitor with IC50 values of 38 nM, 6.6 μM, 6.6 μM and 0.8 μM against mTOR (phospho-S6 cellular assay), PI3Kα, PI3Kγ and PI3Kδ, respectively[1].

  • CAS Number: 1392421-71-4
  • MF: C23H27N7O2
  • MW: 433.51
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Ceralasertib

(S)-Ceralasertib is extracted from patent WO2011154737A1, Compound II, exhibits an IC50 of 2.578 nM[1].(S)-Ceralasertib is a potent and selective sulfoximine morpholinopyrimidine ATR inhibitor with excellent preclinical physicochemical and pharmacokinetic (PK) characteristics.(S)-Ceralasertib is developed improving aqueous solubility and eliminates CYP3A4 time-dependent inhibition[2].

  • CAS Number: 1352226-87-9
  • MF: C20H24N6O2S
  • MW: 412.51
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VX-803 (M4344)

ATR inhibitor 2 is an ATP-competitive, orally active, and selective ATR inhibitor, with a Ki of <150 pM. ATR inhibitor 2 potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (Chk1) phosphorylation with an IC50 of 8 nM. Antitumor activity[1][2].

  • CAS Number: 1613191-99-3
  • MF: C25H29F2N9O3
  • MW: 541.55
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bempedoic acid-d5

Bempedoic acid-d5 is the deuterium labeled Bempedoic acid[1]. Bempedoic acid (ETC-1002) is an ATP-citrate lyase (ACL) inhibitor[1]. Bempedoic acid (ETC-1002) activates AMPK[2].

  • CAS Number: 2408131-71-3
  • MF: C19H31D5O5
  • MW: 349.52
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-7

AKT-IN-7 (compound 1-P1) is a potent AKT inhibitor. AKT-IN-7 has the potential for cancer research[1].

  • CAS Number: 2654025-97-3
  • MF: C23H27ClN6O2
  • MW: 454.95
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(E)-Akt inhibitor-IV

(E)-Akt inhibitor-IV ((E)-AKTIV) is a PI3K-Akt inhibitor, with potent cytotoxic[1].

  • CAS Number: 959841-49-7
  • MF: C31H27IN4S
  • MW: 614.54200
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 165-167 °C
  • Flash Point: N/A

Albanol B

Albanol B is an arylbenzofuran derivative which can be isolated from mulberries. Albanol B exhibits anti-Alzheimer's disease, anti-bacterial and antioxidant activities. Albanol B inhibits cancer cells proliferation, down-regulates CDK1 expression. Albanol B also induces cell cycle arrest at G2/M and apoptosis. And Albanol B induces mitochondrial ROS production and increases the phosphorylation levels of AKT and ERK1/2[1].

  • CAS Number: 87084-99-9
  • MF: C34H22O8
  • MW: 558.53
  • Catalog: Bacterial
  • Density: 1.554g/cm3
  • Boiling Point: 828.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 454.7ºC