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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
H23 IC50 3-7 days Evaluate the inhibitory effect of TH287 on 8-oxodGTPase activity PMC10841254
H2122 IC50 3-7 days Evaluate the effect of TNO155 in combination with MRTX-849 PMC10841254
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. PMC10672174
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. PMC10672174
JH-2-002 300 ng/ml 72 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. PMC10672174
ST8814 300 ng/ml 2 weeks 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. PMC10672174
NCI-H358 10 μmol/L 6 hours Analysis of signaling responses following KRASG12C inhibition identified HER2/HER3 signaling activation as an adaptive resistance mechanism in H358 cells. PMC9394399
NCI-H1792 10 μmol/L 48 hours Analysis of signaling responses following KRASG12C inhibition identified FGFR1 signaling activation as an adaptive resistance mechanism in H1792 cells. PMC10722132
Kelly 2.5±1.7 μmol/L 72 hours To evaluate the effect of SNRPD3 knockdown on cell viability and proliferation, results showed significant reduction in cell viability and proliferation PMC10752212
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 PMC10752212
OSCC cell lines 0.1 μM to 100 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. PMC11550046
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 PMC9319811
H2030 IC50 3-7 days Evaluate the effect of TNO155 in combination with MRTX-849 PMC10841254
NCI-H23 10 μmol/L 48 hours PMC10722132
SK-N-SH 0.6±0.2 μmol/L 72 hours Inhibited neuroblastoma cell proliferation and survival PMC10752212

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
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. PMC10672174
Nude mice KRASG12C-mutated MIA PaCa-2 pancreatic and NCI-H2122 lung cancer cell-derived xenograft models Oral 10, 30, and 100 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. PMC9394399
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. PMC10722132
Zebrafish Neuroblastoma xenograft model Dissolved in water 7.5 or 10 mg/kg Twice per day Evaluate the antitumor activity of TNO155 alone or in combination with ALK-TKIs in neuroblastoma xenografts, results showed combination treatments significantly reduced tumor growth PMC10752212

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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