Cci-779

Base Information

• Chemical Name: Cci-779
• CAS No.: 162635-04-3
• Molecular Formula: C56H87NO16
• Molecular Weight: 1030.3
• Hs Code.: 29349990
• European Community (EC) Number: 686-177-0
• Wikipedia: Temsirolimus
• Wikidata: Q27165485
• NCI Thesaurus Code: C1844
• RXCUI: 657797
• Mol file: 162635-04-3.mol

Synonyms:CCI 779;CCI-779;rapamycin, 42-(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate);temsirolimus;Torisel

Chemical Property of Cci-779

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 99-101 °C
• Refractive Index: 1.553
• Boiling Point: 1048.4 °C at 760 mmHg
• PKA: 10.40±0.70(Predicted)
• Flash Point: 587.8 °C
• PSA: 241.96000
• Density: 1.2 g/cm³
• LogP: 5.66030
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in chloroform, methanol.
• XLogP3: 5.6
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 16
• Rotatable Bond Count: 11
• Exact Mass: 1029.60248569
• Heavy Atom Count: 73
• Complexity: 2010

Purity/Quality:

99% ^*data from raw suppliers

Temsirolimus ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents; Transplant Drugs
• Canonical SMILES: CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OC(=O)C(C)(CO)CO)C)C)O)OC)C)C)C)OC
• Recent EU Clinical Trials: A phase 1B of crizotinib either in combination or as single agent in pediatric patients with ALK, ROS1 or MET positive malignancies
• Description: While renal cell carcinoma (RCC) accounts for only 2 3% of all cancers, the 5-year survival rate for advanced RCC disease is only 5 10%, with approximately 13,000 deaths occurring annually (US statistics only). Immunotherapeutic cytokine options, such as IFN-αand IL-2, have traditionally been frontline treatments, but these agents are not efficacious in all patients and can cause serious side effects. In addition, bevacizumab, a monoclonal antibody against VEGF, has also demonstrated prolongation of PFS. The newest entry for this indication focuses on targets that are downstream from VEGF. Temsirolimus is an inhibitor of the serine/threonine kinase mTOR, which is the mammalian target of rapamycin. mTOR has been implicated in cell replication through control of the cell cycle translation of specific mRNAs. Inhibition of mTOR prevents phosphorylation of the 4E binding protein-1 and the 40S ribosomal protein S6 kinase that are responsible for cell cycle protein translation initiation; cell cycle arrest occurs as the result of termination of cell division from the G1 to the S phase. Disruption of mTOR signaling also has antiangiogenic effects that could be deemed essential in combating RCC, which is driven by unregulated angiogenesis. Temsirolimus is the 2,2-bis(hydroxymethyl)propionate ester of rapamycin (sirolimus), a macrolide fungicide isolated from the bacteria Streptomyces hygroscopicus. Similar to its parent sirolimus, temsirolimus interacts with mTOR through its complex with FK-506 binding protein 12.
• Uses: Temsirolimus, a cell cycle inhibitor developed by Wyeth for the treatment of renal cell carcinoma, was launched in the US in 2007. Temsirolimus works by inhibiting mTOR (mammalian target of rapamycin)-driven cell proliferation. Temsirolimus is also being developed for the treatment of mantle cell lymphoma (PhIII) and also as mono- or combination therapy for the treatment of ovarian and endometrium cancer (PhII). Additionally, temsirolimus is being evaluated for the treatment of several other types of cancer as well as multiple sclerosis and rheumatoid arthritis. Temsirolimus (CCI-779) is a specific mTOR inhibitor with IC50 of 1.76 μM. Temsirolimus is a semisynthetic macrocyclic lactone prepared from rapamycin by selective alkylation of the 42-hydroxy group with a protected bis(dihydromethyl)propionic acid, followed by deprotection. Like all tacrolimus analogues, temsirolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. Temsirolimus is extensively cited in the literature with over 700 citations. Temsirolimus is a semisynthetic macrocyclic lactone prepared from rapamycin by selective acylation of the 42-hydroxy group with a protected bis(dihydromethyl)propionic acid, followed by deprotection. Like all tacrolimus analogues, temsirolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. Temsirolimus is extensively cited in the literature with over 700 citations.
• Clinical Use: Protein kinase inhibitor: Treatment of advanced renal cell carcinoma Treatment of mantle cell lymphoma
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration increased by clarithromycin and telithromycin - avoid; concentration of both drugs increased with erythromycin; concentration of active metabolite reduced by rifampicin and rifabutin - avoid. Antifungals: concentration increased of active metabolite increased by ketoconazole - avoid; concentration increased by fluconazole, itraconazole, miconazole, micafungin, posaconazole and voriconazole - avoid with itraconazole. Antipsychotics: increased risk of agranulocytosis with clozapine - avoid concomitant use. Antivirals: concentration possibly increased by atazanavir, boceprevir and lopinavir; concentration of both drugs increased with telaprevir. Calcium-channel blockers: concentration increased by diltiazem; concentration of both drugs increased with verapamil. Ciclosporin: increased absorption of temsirolimus - give temsirolimus 4 hours after ciclosporin; temsirolimus concentration increased; long term concomitant administration may be associated with deterioration in renal function. Cytotoxics: use crizotinib with caution. Grapefruit juice: concentration of temsirolimus increased - avoid. Mycophenolate: concomitant use of mycophenolate and sirolimus increases plasma levels of both temsirolimus and mycophenolic acid.

Technology Process of Cci-779

There total 60 articles about Cci-779 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

C69H93Cl2NO16 (1296664-73-7) → temsirolimus (162635-04-3,343261-52-9)

Guidance literature:

With sulfuric acid; In tetrahydrofuran; water; at 0 - 30 ℃; for 40.25h;

Reference yield: 100.0%

C68H103NO17 → temsirolimus (162635-04-3,343261-52-9)

Guidance literature:

With sulfuric acid; In tetrahydrofuran; water; at 0 - 30 ℃; for 24.25h;

Reference yield: 93.0%

C62H99NO16Si → temsirolimus (162635-04-3,343261-52-9)

Guidance literature:

With sulfuric acid; water; In tetrahydrofuran; at 0 - 5 ℃;

upstream raw materials:

rapamycin 42-ester with 2,2,5-trimethyl[1,3]dioxane-5-carboxylic acid

3-hydroxy-2-hydroxymethyl-2-methyl-propionic acid vinyl ester

2,2,5-trimethyl-[1,3]dioxane-5-carboxylic acid vinyl ester

2,5-dimethyl-[1,3,2]dioxaborinane-5-carboxylic acid vinyl ester

Downstream raw materials:

C₅₈H₈₈BrNO₁₇

C₆₀H₈₉Br₂NO₁₈

Refernces

• 1、 -. "Preparation method of tansemmus". . . Retrieved 2022/03/18.
• 2、 -. "Intermediate of temsirolimus and preparation method thereof". Paragraph 0062; 0063; 0068. . Retrieved 2019/01/06.