Ipatasertib
CAS No.:
1001264-89-6
M. Wt:
457.996
M. Fa:
C24H32ClN5O2
InChI Key:
GRZXWCHAXNAUHY-NSISKUIASA-N
Appearance:
Off white solid
Names and Identifiers of Ipatasertib
CAS Number |
1001264-89-6 |
|---|---|
EC Number |
825-519-7 |
IUPAC Name |
(2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one |
InChI |
InChI=1S/C24H32ClN5O2/c1-15(2)26-13-19(17-4-6-18(25)7-5-17)24(32)30-10-8-29(9-11-30)23-21-16(3)12-20(31)22(21)27-14-28-23/h4-7,14-16,19-20,26,31H,8-13H2,1-3H3/t16-,19-,20-/m1/s1 |
InChIKey |
GRZXWCHAXNAUHY-NSISKUIASA-N |
Canonical SMILES |
CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O |
Isomeric SMILES |
C[C@@H]1C[C@H](C2=C1C(=NC=N2)N3CCN(CC3)C(=O)[C@H](CNC(C)C)C4=CC=C(C=C4)Cl)O |
UNII |
524Y3IB4HQ |
Physical and chemical properties of Ipatasertib
Acidity coefficient |
13.11±0.40(Predicted) |
|---|---|
Boiling Point |
669.4±55.0 °C at 760 mmHg |
Density |
1.3±0.1 g/cm3 |
Exact Mass |
457.224457 |
Flash Point |
358.7±31.5 °C |
Index of Refraction |
1.603 |
LogP |
1.71 |
Melting Point |
>106°C (dec.) |
Molecular Formula |
C24H32ClN5O2 |
Molecular Weight |
457.996 |
PSA |
81.59000 |
Solubility |
Soluble in DMSO. |
Storage condition |
-20℃ |
Vapour Pressure |
0.0±2.1 mmHg at 25°C |
Water Solubility |
Soluble in DMSO. |
Key Milestone of Ipatasertib
| Time | Milestone Event | Description |
|---|---|---|
| Early 2000s | Discovery and validation of RNA interference (RNAi) mechanism | Andrew Fire and Craig Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering the RNA interference mechanism, laying the scientific foundation for RNAi therapy (including Patisiran). |
| 2006 | Alnylam Pharmaceuticals initiated development of Patisiran | Alnylam started developing a siRNA drug targeting TTR mRNA, using its RNAi platform technology, to treat hereditary transthyretin amyloidosis (hATTR). |
| 2010 | Preclinical studies completed | Patisiran was shown to effectively silence TTR gene expression in animal models, reduce abnormal TTR protein deposition, and improve nerve and heart function. |
| 2013 | Initiation of Phase I clinical trial | First evaluated the safety, tolerability, and pharmacokinetics of Patisiran in healthy volunteers and hATTR patients. |
| 2014 | Initiation of Phase II clinical trial (NCT01961921) | Verified preliminary efficacy in hATTR polyneuropathy patients. Results showed significant reduction in TTR protein levels and stabilization of neurological function. |
| 2015 | Initiation of Phase III clinical trial (APOLLO study, NCT01960348) | A global, multi-center, randomized, double-blind, placebo-controlled trial involving 225 hATTR polyneuropathy patients. |
| 2017 | Results of APOLLO study published | Patisiran significantly improved neuropathy, quality of life, and walking ability, and reduced TTR levels by over 80%, with good safety profile. |
| August 2018 | Approved by the U.S. FDA | Patisiran (marketed as Onpattro®) became the first approved RNAi therapeutic drug globally, used to treat adult patients with hATTR with polyneuropathy. |
| November 2018 | Approved by the EMA in the EU | Approved in Europe for the same indication. |
| 2019 onwards | Approval in multiple countries worldwide | Patisiran was subsequently approved in Japan, Canada, Brazil, and other countries. |
| 2020s | Expansion of indications research | Conducted clinical trials (e.g., APOLLO-B study) to explore new applications, such as hATTR cardiomyopathy. |
| 2022 | Results of APOLLO-B Phase III study published | Results showed that Patisiran improved cardiac function and survival in patients with hATTR cardiomyopathy, supporting the application for new indications. |
Applications of Ipatasertib
Ipatasertib is primarily explored for its application in oncology. It is being studied for the treatment of various solid tumors, including:
- Breast Cancer
- Gastric Cancer
- Uterine Serous Carcinoma
- Triple-Negative Breast Cancer
Its role as a targeted therapy aims to improve treatment outcomes in patients whose tumors exhibit aberrations in the PI3K/AKT/mTOR pathway.
Physical sample testing spectrum (NMR) of Ipatasertib
Cas:1001270-64-9
