TIC10
- Product Name
- TIC10
- CAS No.
- 1616632-77-9
- Chemical Name
- TIC10
- Synonyms
- imipridone;TIC10;ONC201;CS-2579;ONC201,TIC10;dordaviprone;TIC-10 (ON201);TIC10(ONC-201);ONC201 dordaviprone;TIC 10 active isomer
- CBNumber
- CB12711459
- Molecular Formula
- C24H26N4O
- Formula Weight
- 386.49
- MOL File
- 1616632-77-9.mol
TIC10 Property
- Boiling point:
- 559.7±60.0 °C(Predicted)
- Density
- 1.24±0.1 g/cm3(Predicted)
- storage temp.
- Sealed in dry,Store in freezer, under -20°C
- solubility
- Soluble in DMSO (up to 25 mg/ml with warming).
- pka
- 6.38±0.20(Predicted)
- form
- solid
- color
- Pale yellow
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
- InChI
- InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-23(29)21-17-26(15-19-8-3-2-4-9-19)13-11-22(21)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3
- InChIKey
- VLULRUCCHYVXOH-UHFFFAOYSA-N
- SMILES
- C12=NCCN1C1CCN(CC3=CC=CC=C3)CC=1C(=O)N2CC1=CC=CC=C1C
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P264Wash hands thoroughly after handling.
P264Wash skin thouroughly after handling.
P271Use only outdoors or in a well-ventilated area.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P302+P352IF ON SKIN: wash with plenty of soap and water.
P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P312Call a POISON CENTER or doctor/physician if you feel unwell.
P321Specific treatment (see … on this label).
P332+P313IF SKIN irritation occurs: Get medical advice/attention.
P337+P313IF eye irritation persists: Get medical advice/attention.
P362Take off contaminated clothing and wash before reuse.
P403+P233Store in a well-ventilated place. Keep container tightly closed.
P405Store locked up.
P501Dispose of contents/container to..…
N-Bromosuccinimide Price
- Product number
- 16109
- Product name
- TIC10
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $32
- Updated
- 2024/03/01
- Product number
- 16109
- Product name
- TIC10
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $109
- Updated
- 2024/03/01
- Product number
- 16109
- Product name
- TIC10
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $199
- Updated
- 2024/03/01
- Product number
- 16109
- Product name
- TIC10
- Purity
- ≥98%
- Packaging
- 25mg
- Price
- $420
- Updated
- 2024/03/01
- Product number
- B285480
- Product name
- 7-Benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one
- Packaging
- 50mg
- Price
- $160
- Updated
- 2021/12/16
TIC10 Chemical Properties,Usage,Production
Description
TIC10 induces the expression of TNF-related apoptosis-inducing ligand (TRAIL) at 1-5 μM in a p53-independent manner. It is orally active, stable, and crosses the blood-brain barrier. The induction of TRAIL results from dual inhibition of Akt and ERK1/2 combined with nuclear translocation of the transcription factor FOXO3a. TIC10 suppresses the growth of orthotopic human glioblastoma multiforme tumors in mice.
Uses
7-Benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one is used in biological studies for structure confirmation and pharmacophore reassignment for induction of immunosurveillance cytokine TRAIL in macrophages. The structure of this compound was misassigned for many years as H291055. The resolution of this issue was recently highlighted in Chemical and Engeneering News 92(23) 32 (2014).
Biological Activity
TIC10 (also named ONC21), a first-in-class small molecule inducer of TRAIL, has been developed. Preclinical studies have shown that it potently induces TRAIL expression. TIC10 treatment in cancer cells blocks Akt and Erk signalling to activate Foxo3a, which transcriptionally up-regulates the TRAIL gene. TIC10 has displayed ideal properties as a potential anti-cancer drug, including a broad spectrum of activity, wide safety margin, robust stability, aqueous solubility, favourable pharmacokinetics, and oral activity[5].
Synthesis
38941-29-6
3939-01-3
1616632-77-9
N-(2-methylbenzyl)-4,5-dihydro-1H-imidazol-2-amine (7) (795 mg, 4.2 mmol) and 1-benzyl-3-methoxycarbonyl-piperidin-4-one hydrochloride (8) (568 mg, 2.0 mmol) were used as raw materials and reacted in a methanolic solution of sodium methanolate (0.5 M, 3.0 mL, 1.5 mmol). The reaction mixture was stirred under mild reflux conditions for 18 hours. Upon completion of the reaction, it was cooled to room temperature, diluted with dichloromethane (50 mL) and subsequently washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. Purification by silica gel column chromatography (eluent ratio 19:1 dichloromethane/methanol) afforded the target product 7-benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one (2) (753 mg, 97% yield) as a light yellow solid. Melting point: 132-135°C (methanol). Thin layer chromatography Rf value: 0.25 (silica gel, 19:1 dichloromethane/methanol). IR spectrum (pure) vmax: 2750, 2358, 1646, 1616, 1487, 1296, 738 cm-1. 1H NMR (500 MHz, CDCl3) δ: 7.33 (m, 5H), 7.11 (m, 4H), 5.05 (s, 2H), 3.89 (m, 4H), 3.67 (s, 2H). 3.32 (s, 2H), 2.68 (m, 2H), 2.51 (m, 2H), 2.40 (s, 3H).13C NMR (150 MHz, CDCl3) δ: 161.6, 153.4, 145.8, 137.7, 135.7, 134.4, 130.4, 129.3, 128.6, 127.5, 127.0, 126.0, 125.4, 102.1, 62.5, 50.7, 49.7, 48.3, 47.1, 43.3, 27.0, 19.4. Calculated value by high-resolution mass spectrometry (ESI-TOF): C24H26N4OH + [M + H]+ 387.2179, measured value: 387.2166.
in vitro
TIC10/ONC201, a first-in-class small-molecule inducer of tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). The in vitro results showed that TIC10 induced potent cytotoxic and cytostatic activities in several human pancreatic cancer cell lines (Panc-1, Mia-PaCa2, AsPC-1 or L3.6). TIC10 activated both extrinsic (TRAIL-caspase-8-dependent) and endogenous/mitochondrial (caspase-9-dependent) apoptosis pathways in the pancreatic cancer cells. Molecularly, TIC10 inhibited Akt-Erk activation yet induced TRAIL expression in pancreatic cancer cells. Significantly, TIC10, at a relatively low concentration, sensitized gemcitabine-induced growth inhibition and apoptosis against pancreatic cancer cells. Further, TIC10 and gemcitabine synergistically inhibited Panc-1 xenograft growth in SCID mice. The combination treatment also significantly improved mice survival. In addition, Akt-Erk in-activation and TRAIL/cleaved-caspase-8 induction were observed in TIC10-treated Panc-1 xenografts[5].
References
1) Allenet al.(2013)Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects, Sci. Transl. Med.5171ra17
2) Allenet al.(2015)Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway,Mol. Cancer.1499
3) Allenet al.(2016)Discovery and Clinical Introduction of First-In-Class Imipridone ONC201, Oncotarget774380
4) Ishizawaet al.(2019)Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality, Cancer Cell35721
[6] Qiangbo Zhang . “The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.” Biochemical and biophysical research communications 476 4 (2016): Pages 260-266.
TIC10 Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from TIC10 manufacturers
- Product
- TIC10 1616632-77-9
- Price
- US $0.00/gram
- Min. Order
- 1gram
- Purity
- 99%
- Supply Ability
- 10kg
- Release date
- 2022-02-18
- Product
- 4-[5-methyl-4-[(4-methylphenyl)sulfonylmethyl]-1,3-oxazol-2-yl]-N-(pyridin-3-ylmethyl)benzamide 1616632-77-9
- Price
- US $1.00/KG
- Min. Order
- 1KG
- Purity
- Min98% HPLC
- Supply Ability
- g/kg/ton
- Release date
- 2020-01-01