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Chemical Structure| 1345847-93-9 Chemical Structure| 1345847-93-9

Structure of Altiratinib
CAS No.: 1345847-93-9

Chemical Structure| 1345847-93-9

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Altiratinib is a c-MET/TIE-2/VEGFR inhibitor which effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro.

Synonyms: DCC-2701

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Product Details of Altiratinib

CAS No. :1345847-93-9
Formula : C26H21F3N4O4
M.W : 510.46
SMILES Code : O=C(C1(C(NC2=CC=C(F)C=C2)=O)CC1)NC3=CC(F)=C(OC4=CC(NC(C5CC5)=O)=NC=C4)C=C3F
Synonyms :
DCC-2701
MDL No. :MFCD28900672

Safety of Altiratinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Altiratinib

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Ba/F3 TPM3-NTRK1G667S 93.5 nM 72 h Evaluate the inhibitory effect of Altiratinib on TPM3-NTRK1G667S mutant cells, results show IC50 of 93.5 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 TPM3-NTRK1G667C 1.8 nM 72 h Evaluate the inhibitory effect of Altiratinib on TPM3-NTRK1G667C mutant cells, results show IC50 of 1.8 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 TPM3-NTRK1F589L 18.3 nM 72 h Evaluate the inhibitory effect of Altiratinib on TPM3-NTRK1F589L mutant cells, results show IC50 of 18.3 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 TPM3-NTRK1V573M 2.8 nM 72 h Evaluate the inhibitory effect of Altiratinib on TPM3-NTRK1V573M mutant cells, results show IC50 of 2.8 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 ETV6-NTRK3G623R 240 nM 72 h Evaluate the inhibitory effect of Altiratinib on ETV6-NTRK3G623R mutant cells, results show partial sensitivity with IC50 of 240 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 ETV6-NTRK3 7.3 nM 72 h Evaluate the inhibitory effect of Altiratinib on ETV6-NTRK3 fusion-driven cells, results show IC50 of 7.3 nM Commun Biol. 2020 Dec 16;3(1):776.
Ba/F3 TPM3-NTRK1 11.3 nM 72 h Evaluate the inhibitory effect of Altiratinib on TPM3-NTRK1 fusion-driven cells, results show IC50 of 11.3 nM Commun Biol. 2020 Dec 16;3(1):776.
GSC6-27, GSC7-2, GSC11, GSC17, GSC231, GSC295, GSC20, GSC300, GSC28, GSC272, GSC8-11, GSC262, GSC23, GSC280 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM 72 h Determination of cell viability and IC50 Neuro Oncol. 2016 Sep;18(9):1230-41.
Ba/F3 cells 100 nM 72 h Screening for drugs that inhibit MET D1228A/Y secondary mutations, found that Altiratinib and other four type II MET-TKIs showed growth inhibition below 50% J Hematol Oncol. 2022 Jun 11;15(1):79.
Mouse melanocytes (Mel-Ab) 0.01–1 µM 72 h To evaluate the effect of Altiratinib on melanogenesis. Results showed that Altiratinib inhibited FSK-stimulated nuclear localization of CRTC3 by increasing its phosphorylation, thereby reducing melanogenesis. Theranostics. 2021 Oct 17;11(20):9918-9936.
Normal human epidermal melanocytes (NHM) 0.01–1 µM 72 h To evaluate the effect of Altiratinib on melanogenesis. Results showed that Altiratinib dose-dependently suppressed FSK-stimulated CREB transcriptional activity and reduced melanin content without affecting cell viability. Theranostics. 2021 Oct 17;11(20):9918-9936.
GIC lines (G88 and G528) 0–2.5 μM 72 h To evaluate the effects of altiratinib and abemaciclib alone and in combination on GIC cell viability, showing significant synergy in combination therapy. Cancer Res. 2018 Aug 1;78(15):4360-4369.
mouse melanocytes (Mel-Ab) 1 µM 72 h Evaluate effects on tyrosinase activity Clin Transl Med. 2024 Mar;14(3):e1625.
normal human melanocytes (NHM) 10 µM 72 h Evaluate cytotoxicity and melanogenesis inhibition Clin Transl Med. 2024 Mar;14(3):e1625.
B16F10 mouse melanoma cells 1 µM 72 h Evaluate inhibitory effects on CRTC3 activity and melanogenesis Clin Transl Med. 2024 Mar;14(3):e1625.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mouse NIH3T3 ETV6-NTRK3 xenograft model Oral 15 mg/kg Once daily, continuous treatment Evaluate the inhibitory effect of Altiratinib on ETV6-NTRK3 fusion-driven tumors, results show significant tumor growth inhibition Commun Biol. 2020 Dec 16;3(1):776.
Nude mice GSC11 and GSC17 xenograft mouse models Oral gavage 10 mg/kg Twice daily, continuous treatment Evaluate the effects of Altiratinib alone or in combination with bevacizumab on tumor growth, invasiveness, angiogenesis, and TIE2-expressing monocyte infiltration Neuro Oncol. 2016 Sep;18(9):1230-41.
BALB/c SCID NCr mice Orthotopic GBM xenograft model Oral gavage 40 mg/kg; 60 mg/kg Continuous treatment: abemaciclib 6 days/week, altiratinib daily; Alternating treatment: each drug alternating 3 days on and 3 days off To evaluate the efficacy of altiratinib and abemaciclib alone and in combination in an orthotopic GBM xenograft model, showing that the combined treatment significantly prolonged median and overall survival. Cancer Res. 2018 Aug 1;78(15):4360-4369.
KRT14-SCF transgenic mice Skin hyperpigmentation model Topical application 10 µM Not specified Evaluate inhibition of epidermal melanin and tyrosinase protein levels Clin Transl Med. 2024 Mar;14(3):e1625.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.80mL

1.96mL

0.98mL

19.59mL

3.92mL

1.96mL

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

References

 

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