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Chemical Structure| 1809427-19-7 Chemical Structure| 1809427-19-7

Structure of DT-061
CAS No.: 1809427-19-7

Chemical Structure| 1809427-19-7

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DT-061 is an oral activator of protein phosphatase 2A (PP2A). DT-061 can be used in the treatment of kras mutation and MYC-driven tumorigenesis.

Synonyms: SMAP

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Product Details of DT-061

CAS No. :1809427-19-7
Formula : C25H23F3N2O5S
M.W : 520.52
SMILES Code : O=S(C1=CC=C(OC(F)(F)F)C=C1)(N[C@H]2[C@H](O)[C@@H](N3C4=C(C=CC=C4)OC5=CC=CC=C35)CCC2)=O
Synonyms :
SMAP
MDL No. :MFCD31813712

Safety of DT-061

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HeLa 20 µM 2 h PMC9289710
MV4-11 cells 10 μM 48 hours Evaluate the inhibitory effect of PLX51107 on FLT3-ITD mutated AML cells PMC8027945
Preosteoclasts 1 day Measure PP2A activity PMC10417323
H358 cells 30 μM 1-2 hours To assess the dependency of PP2A activity on MEK inhibitor responses PMC7243596
H441 cells 10 μM 24 hours To assess the dependency of PP2A activity on MEK inhibitor responses PMC8335581
H358 cells 10 μM 24 hours To assess the dependency of PP2A activity on MEK inhibitor responses PMC8335581
H293T cells 20 or 30 μM 1 hour To directly test the effect of DT-061 on B56α trimers using the NanoBRET system, results showed an increase in B56α-specific PP2A trimerization upon DT-061 treatment PMC7243596
A549 cells 72 hours Inhibited RSK4 activation, resulting in decreased cellular cIAP1 and cIAP2 expression PMC8335581
Bax/Bak double-knockout MEC1 cells 12, 16, 20 μM 12 hours To validate that DT-061 can induce apoptosis even in the absence of Bax/Bak, results showed that DT-061 induced apoptosis via the mPTP pathway. PMC10313372
Chronic lymphocytic leukemia cells 12, 16, 20 μM 18 hours To evaluate the inhibitory effect of BOC-D-FMK on CFZ-induced apoptosis. Results showed that BOC-D-FMK significantly reduced CFZ-induced PARP cleavage and apoptosis. PMC10313372
HEK-293T 20 µM 30 min To detect the effect of DT-061 on PP2A-B56 complexes, no binding or activity changes were observed PMC9289710
Human aortic smooth muscle cells (SMCs) 5 μM 24 hours To evaluate the effect of DT-061 on PDGF-induced proliferation of SMCs. Results showed that DT-061 significantly inhibited PDGF-induced proliferation of SMCs. PMC10922415
Human aortic smooth muscle cells (SMCs) 5 μM 12 hours To evaluate the effect of DT-061 on PDGF-induced proliferation of SMCs. Results showed that DT-061 significantly inhibited PDGF-induced proliferation of SMCs. PMC10922415
Chronic lymphocytic leukemia cells 15 μM 24 hours To evaluate the inhibitory effect of BOC-D-FMK on CFZ-induced apoptosis. Results showed that BOC-D-FMK significantly reduced CFZ-induced PARP cleavage and apoptosis. PMC9436923
FLT3-ITD AML primary cells 10 μM 48 hours Enhanced FLT3 inhibitor apoptosis induction in FLT3-ITD AML primary cells PMC8027945
Ba/F3-ITD cells 10 μM 48 hours To evaluate the cytotoxicity and apoptosis induction effects of TP-3654 in combination with gilteritinib, results showed that the combination treatment significantly increased apoptosis induction. PMC8027945
DAOY 10 μM 72 hours Abacavir alone decreased the clonogenic survival of DAOY cells and showed synergistic effects when combined with 5-aza-dC and IR. PMC10483611
E98 10 μM 72 hours Long-term growth assays demonstrated that triplet therapy (AKTi + PDKi + PP2A reactivator) led to cytotoxic apoptosis, preventing escape from therapy. PMC10483611
T98G 10 μM 24 hours Evaluated the effect of PP2A reactivation on cell growth, showing significant growth inhibition and apoptosis induction when combined with UCN-01. PMC10483611
Pcdh7-deficient mouse bone marrow-derived monocytes 10 µM 24 hours Failed to restore impaired cell migration PMC11766416
Wild-type mouse bone marrow-derived monocytes 10 µM 24 hours Enhanced cell migration PMC11766416

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice H358 lung cancer xenograft model 5 mg/kg subcutaneous injection Twice daily for 29 days To evaluate the effect of DT-061 on B56α-PP2A heterotrimer composition, results showed a significant increase, roughly two-fold, in B56α trimers after DT-061 treatment PMC7243596
Nude mice H358 and H441 xenograft models 5 mg/kg Oral gavage Once daily for 4 weeks To evaluate the antitumor effect of DT-061 in combination with MEK inhibitor AZD6244 in KRAS-driven lung cancer models PMC8335581
Rag2−/−γC−/− mice CLL xenograft model 15 mg/kg oral gavage Twice daily, continuous treatment To evaluate the antitumor efficacy of DT-061 in vivo, results showed that DT-061 significantly inhibited the growth of both WT and Bax/Bak-DKO CLL cells, independent of the Bax/Bak pathway. PMC10313372
Mice (C57BL/6) Mouse heterotopic heart transplantation model 5 mg/kg Oral gavage Twice daily, starting on the day of transplantation until the completion of experiments To evaluate the effect of DT-061 on heart transplant rejection in mice. Results showed that DT-061 significantly prolonged cardiac allograft survival and alleviated acute cardiac rejection. PMC10922415
Mice Eµ-TCL1 chronic lymphocytic leukemia model 5 mg/kg Oral gavage Once daily for 28 days To evaluate the effect of DT-061 on CLL cell burden in vivo, results showed that DT-061 reduced leukemic burden in peripheral blood, spleen, and bone marrow, accompanied by a decrease in N1-ICD expression. PMC9436923
NSG mice MV4-11-luc xenograft model 5 mg/kg Intravenous injection Every other day starting from Day 7 post-inoculation DT-061 enhanced gilteritinib's growth suppression in MV4-11-luc xenograft model PMC8027945
Mice Pcdh7-deficient mice 10 μM 3 days Rescued impaired RhoA activation and osteoclast differentiation in Pcdh7?/? cells PMC10417323

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.61mL

1.92mL

0.96mL

19.21mL

3.84mL

1.92mL

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
 

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