[CAS NO. 1801765-04-7] Batoprotafib
PRODUCTS SPECIFICATIONS [1801765-04-7]
DESCRIPTION [1801765-04-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 421.95 |
| Molecular Formula | C18H24ClN7OS |
| SMILES | N[C@@H]1[C@H](C)OCC12CCN(C3=NC(N)=C(SC4=C(Cl)C(N)=NC=C4)N=C3)CC2 |
1 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 0.011 µM (SHP2) [1]
In Vitro
Batoprotafib shows an IC
50
of 0.008 µM in KYSE520 pERK assay and shows an IC
50
of 0.100 µM in KYSE520 5-day cell proliferation assay. The off-target IC
50
values are 18 µM, 6.9 µM, and 11 µM for Cav1.2, VMAT, and SST3, respectively
[1]
.
Batoprotafib (0-1000 nM; 6 days) inhibits the viability of NCI-H3255, HCC827, and PC9 cells with IC
50
values lower than 1.5 μM. Batoprotafib is efficacious in EGFR-mutant NSCLC cell lines
[2]
.
Batoprotafib is efficacious in acquired resistance models of EGFR inhibitors and demonstrates combination benefit with EGFR inhibitors
[2]
.
Batoprotafib enhances the efficacy of KRAS
G12C
inhibitors against KRAS
G12C
lung and colorectal cancers
[2]
.
Batoprotafib inhibits immune-suppressive macrophages and synergizes with PD1 blockade
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [2]
| Cell Line: | PC-9, PC-9 EGFR T790M/C797S , HCC827, HCC827-GR (gefinitib-resistant) |
| Concentration: | 0-1000 nM |
| Incubation Time: | 6 days |
| Result: | Inhibited cell viability with IC 50 s of 1.56, 1.38, 0.77 and 1.38 μM against PC-9 and PC-9 EGFR T790M/C797S , HCC827 and HCC827-GR cells, respectively. |
Western Blot Analysis [2]
| Cell Line: | PC-14 (EGFR ex19del ) |
| Concentration: | 3 μM |
| Incubation Time: | 4h and 24 h |
| Result: | Effectively reduced p-ERK levels at 4 hours but suffered a rebound at 24 hours. |
In Vivo
The oral bioavailability in mouse, rat and money are 78%, 86%, and 60%, respectively
[1]
.
Batoprotafib (20 mg/kg; p.o.; twice daily for 40 days) inhibits tumor growth and is more effective when combined with
Dabrafenib
(HY-14660) plus
Trametinib
(HY-10999) in nude mice bearing HT-29 xenografts
[2]
.
Batoprotafib (7.5 mg/kg; p.o.; b.i.d. or q.d. for 36 days) plus
JDQ-443
(HY-139612) (100 mg/kg; p.o.; q.d.) improves the single-agent activity of JDQ443 in
KRAS
G12C
-mutated cell-derived (CDX) models in nude mice
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female athymic nude mice bearing HT-29 xenografts [2] |
| Dosage: | 20 mg/kg alone or 10 mg/kg in combination with Dabrafenib and Trametinib |
| Administration: | PO, twice daily for 40 days |
| Result: | Resulted in moderate tumor growth inhibition. Maintained tumor stasis for more than 40 days when combined with Dabrafenib plus Trametinib. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04000529 | Novartis Pharmaceuticals|Novartis |
Non-small Cell Lung Carcinoma|Head and Neck Squamous Cell Carcinoma|Esophageal SCC|Gastrointestinal Stromal Tumors|Colorectal Cancer
|
July 30, 2019 | Phase 1 |
| NCT03114319 | Novartis Pharmaceuticals|Novartis |
Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head+Neck SCC,Melanoma
|
May 26, 2017 | Phase 1 |
| NCT05541159 | Novartis Pharmaceuticals|Pharmaceutical Research Associates|Novartis |
Renal Impairment
|
November 30, 2022 | Phase 1 |
| NCT04294160 | Novartis Pharmaceuticals|Novartis |
BRAF V600 Colorectal Cancer
|
July 22, 2020 | Phase 1 |
| NCT04185883 | Amgen |
Advanced Solid Tumors|Kirsten Rat Sarcoma (KRAS) pG12C Mutation
|
December 17, 2019 | Phase 1|Phase 2 |
| NCT04330664 | Mirati Therapeutics Inc.|Novartis |
Advanced Cancer|Metastatic Cancer|Malignant Neoplastic Disease
|
April 22, 2020 | Phase 1|Phase 2 |
| NCT05490030 | Novartis Pharmaceuticals|Pharmaceutical Research Associates|Novartis |
Hepatic Impairment
|
November 24, 2022 | Phase 1 |
| NCT04699188 | Novartis Pharmaceuticals|Novartis |
KRAS G12C Mutant Solid Tumors|Carcinoma, Non-Small-Cell Lung|Carcinoma, Colorectal|Cancer of Lung|Cancer of the Lung|Lung Cancer|Neoplasms, Lung|Neoplasms, Pulmonary|Pulmonary Cancer|Pulmonary Neoplasms
|
February 24, 2021 | Phase 1|Phase 2 |
| NCT04292119 | Massachusetts General Hospital|Array BioPharma|Pfizer |
Lung Cancer|Anaplastic Lymphoma Kinase Gene Translocation|ROS1 Rearrangement|Relapsed Cancer|MET Amplification|Resistant Cancer|NSCLC
|
May 1, 2020 | Phase 1|Phase 2 |
| NCT04956640 | Eli Lilly and Company|Loxo Oncology, Inc.|Merck Sharp & Dohme LLC |
Carcinoma, Non-Small-Cell Lung|Colorectal Neoplams|Endometrial Neoplasms|Ovarian Neoplasms|Pancreatic Neoplasms
|
July 19, 2021 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 236.99 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3699 mL | 11.8497 mL | 23.6995 mL |
| 5 mM | 0.4740 mL | 2.3699 mL | 4.7399 mL |
| 10 mM | 0.2370 mL | 1.1850 mL | 2.3699 mL |
References
- [1] TNO155: SHP2 inhibitor
- [2] Liu C, et al. Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling. Clin Cancer Res. 2021 Jan 1;27(1):342-354.
- [3] Weiss A, et al. Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022 Jun 2;12(6):1500-1517.