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Chemical Structure| 2086772-26-9 Chemical Structure| 2086772-26-9

Structure of Onametostat
CAS No.: 2086772-26-9

Chemical Structure| 2086772-26-9

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JNJ-64619178 is a selective, orally active, and pseudo-irreversible inhibitor of protein arginine methyltransferase 5 (IC50: 0.14 nM). It has effective activity In lung cancer.

Synonyms: JNJ-64619178

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Product Citations

Product Citations

Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.

Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.

Alternative Products

Product Details of Onametostat

CAS No. :2086772-26-9
Formula : C22H23BrN6O2
M.W : 483.36
SMILES Code : O[C@@H]1[C@H](O)[C@@H](CCC2=CC3=C(C=C(Br)C(N)=N3)C=C2)C[C@]1(N4C=CC5=C(N)N=CN=C45)[H]
Synonyms :
JNJ-64619178
MDL No. :MFCD31813596
InChI Key :DBSMLQTUDJVICQ-CJODITQLSA-N
Pubchem ID :126637809

Safety of Onametostat

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H332-H372-H400
Precautionary Statements:P260-P264-P270-P273-P280-P301+P312+P330-P304+P312-P305+P351+P338-P314-P337+P313-P391-P501
Class:9
UN#:3077
Packing Group:

Related Pathways of Onametostat

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Plasmodium falciparum 3D7 1.69 ± 0.04 µM (IC50) 72 hours To evaluate the inhibitory effect of Onametostat on the asexual growth of malaria parasites, results showed Onametostat exhibited the strongest antimalarial activity. PMC11459956
A549 0.2 nmol/L Evaluate cytotoxicity, showing low cytotoxicity PMC9398174
NCI-H1048 1-10 nmol/L 48-96 hours Inhibition of PRMT5 activity, reduction of SmD1/3 dimethylation levels PMC9398174
U87-MG cells 10 µM 1hr To evaluate the effect of JNJ-64619178 on DNA damage repair, results showed JNJ-64619178 significantly inhibited DNA damage repair PMC10028149
A549 cells 10 µM 1hr Inhibited RSK4 activation, resulting in decreased cellular cIAP1 and cIAP2 expression PMC10028149
DU145 cells 100 nM 4 Days To evaluate the effect of JNJ-64619178 on DNA damage repair, results showed JNJ-64619178 significantly inhibited DNA damage repair PMC10028149
LNCaP cells 1 µM 4 Days To evaluate the effect of JNJ-64619178 on DNA damage repair, results showed JNJ-64619178 significantly inhibited DNA damage repair PMC10028149

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice NCI-H1048 lung cancer xenograft model Oral 0.1-10 mg/kg 6 consecutive days Inhibition of tumor growth, reduction of SmD1/3 dimethylation levels PMC9398174
Nude mice SU-CCS-1 xenograft model Intraperitoneal injection 10 mg/kg Once daily for 5 weeks Evaluate the inhibitory effect of JNJ-64619178 on tumor growth PMC9513783

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03573310 Neoplasms|Solid Tumor, Adult|N... More >>on-Hodgkin Lymphoma|Myelodysplastic Syndromes Less << PHASE1 ACTIVE_NOT_RECRUITING 2025-12-31 Florida Specialist and Cancer ... More >>Institute, Sarasota, Florida, 34232, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Ohio State University, Columbus, Ohio, 43210, United States|University of Texas, MD Anderson Cancer Center, Houston, Texas, 77030, United States|St. Paul's Hospital, Vancouver, British Columbia, V6E 1M7, Canada|Princess Margaret Cancer Centre University Health Network, Toronto, Ontario, M5G1Z5, Canada|Universitaetsklinikum Duesseldorf, Düsseldorf, 40225, Germany|Goethe Universit?t Frankfurt, Frankfurt/Main, 60590, Germany|Universitaetsklinikum Leipzig, Leipzig, 04103, Germany|Carmel Medical Center, Haifa, 34362, Israel|Hadassah Medical Center, Jerusalem, 9112001, Israel|Tel Aviv Sourasky MC, Tel Aviv, 6423906, Israel|Hosp. Univ. Germans Trias I Pujol, Badalona, 08916, Spain|Hosp Univ Vall D Hebron, Barcelona, 08035, Spain|Hosp Univ Fund Jimenez Diaz, Madrid, 28040, Spain|Clinica Univ. de Navarra, Pamplona, 31008, Spain|Hosp Clinico Univ de Salamanca, Salamanca, 37007, Spain|Hosp. Virgen Del Rocio, Sevilla, 41013, Spain Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.07mL

0.41mL

0.21mL

10.34mL

2.07mL

1.03mL

20.69mL

4.14mL

2.07mL

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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