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Chemical Structure| 1801765-04-7 Chemical Structure| 1801765-04-7

Structure of Batoprotafib
CAS No.: 1801765-04-7

Chemical Structure| 1801765-04-7

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TNO155 is a potent selective and orally active allosteric inhibitor of wild-type SHP2 (IC50=0.011 µM). TNO155 has the potential for the study of RTK-dependent malignancies, especially advanced solid tumors[1].

Synonyms: TNO155

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Product Details of Batoprotafib

CAS No. :1801765-04-7
Formula : C18H24ClN7OS
M.W : 421.95
SMILES Code : N[C@@H]1[C@@H](OCC12CCN(CC2)C3=NC(N)=C(N=C3)SC4=C(C(N)=NC=C4)Cl)C
Synonyms :
TNO155
MDL No. :MFCD32693919
InChI Key :UCJZOKGUEJUNIO-IINYFYTJSA-N
Pubchem ID :118238370

Safety of Batoprotafib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Batoprotafib (TNO155) is a highly potent, selective, and orally active allosteric inhibitor of wild-type SHP2, with an IC50 of 0.011 µM. It holds promise for investigating RTK-dependent malignancies, particularly advanced solid tumors [1].

In Vitro:

Cell Line
Concentration Treated Time Description References
OSCC cell lines 3 μM 72 hours To evaluate the inhibitory effect of TNO155 on OSCC cell lines, results showed that TNO155 exhibited high efficacy in most OSCC cell lines, with IC50 ranging from 0.39 μM to 211.1 μM. Heliyon. 2024 Oct 22;10(21):e39677.
JH-2-002 0.3 μM 48 hours To evaluate the effect of TNO155 on cell cycle and apoptosis-related proteins, results showed that TNO155 significantly inhibited cell cycle regulators and inhibitor-of-apoptosis proteins. Sci Adv. 2023 Nov 24;9(47):eadg8876.
ST8814 30-3000 nM 24 hours To evaluate the effect of TNO155 on ERK signaling pathway and cell cycle regulators, results showed that TNO155 dose-dependently inhibited ERK signaling pathway and cell cycle regulators. Sci Adv. 2023 Nov 24;9(47):eadg8876.
Kelly 2.5±1.7 μmol/L 72 hours Evaluate the sensitivity of ALK-mutant neuroblastoma cells to TNO155, results showed ALK-mutant cells were more sensitive to TNO155 Cancer Res Commun. 2023 Dec 27;3(12):2608-2622.
LAN-6 1.1±0.4 μmol/L 72 hours Evaluate the sensitivity of ALK-mutant neuroblastoma cells to TNO155, results showed ALK-mutant cells were more sensitive to TNO155 Cancer Res Commun. 2023 Dec 27;3(12):2608-2622.
SK-N-SH 0.6±0.2 μmol/L 72 hours Evaluate the sensitivity of ALK-mutant neuroblastoma cells to TNO155, results showed ALK-mutant cells were more sensitive to TNO155 Cancer Res Commun. 2023 Dec 27;3(12):2608-2622.
AZDR14 cells 1 µM 24 hours TNO155 inhibited GAB1 phosphorylation and disrupted the association between SHP2 and GAB1, thereby inhibiting the ERK1/2 signaling pathway Cells. 2022 Jul 14;11(14):2201.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice KRASG12C-mutated MIA PaCa-2 pancreatic and NCI-H2122 lung cancer cell-derived xenograft models Oral 10 mg/kg Once or twice daily until the end of the experiment To evaluate the antitumor activity of JDQ443 in KRASG12C-mutated tumor models, results showed dose-dependent inhibition of tumor growth. Cancer Discov. 2022 Jun 2;12(6):1500-1517.
NRG mice MPNST PDX model Oral gavage 7.5 mg/kg TNO155 twice daily, ribociclib once daily, for 4 weeks To evaluate the effect of TNO155 alone or in combination with ribociclib on tumor growth in MPNST PDX models, results showed that TNO155 alone exhibited significant antitumor activity in some models, while the combination showed deeper antitumor effects in partially sensitive models. Sci Adv. 2023 Nov 24;9(47):eadg8876.
Mouse LU99 (KRASG12C NSCLC) xenograft model Oral 10 mg/kg BID Twice daily for 21 days Evaluate the effect of TNO155 alone and in combination with JDQ443 on LU99 tumor growth, showing combination treatment significantly extended the duration of tumor responses. Cancer Res. 2023 Dec 15;83(24):4130-4141.
Zebrafish Neuroblastoma xenograft model Dissolved in water 5 or 10 μmol/L 72 hours Evaluate the antitumor activity of TNO155 alone or in combination with ALK-TKIs in neuroblastoma xenografts, results showed combination treatments significantly reduced tumor growth Cancer Res Commun. 2023 Dec 27;3(12):2608-2622.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05490030 Hepatic Impairment PHASE1 WITHDRAWN 2025-06-26 -
NCT05541159 Renal Impairment PHASE1 WITHDRAWN 2025-07-15 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.85mL

2.37mL

1.18mL

23.70mL

4.74mL

2.37mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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