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Details

Stereochemistry ACHIRAL
Molecular Formula C15H25N2.C7H7O3S
Molecular Weight 404.566
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ASM-024

SMILES

CC1=CC=C(C=C1)S([O-])(=O)=O.CC[N+]2(CC)CCCN(CC2)C3=CC=CC=C3

InChI

InChIKey=PXRYYARWCNIUKT-UHFFFAOYSA-M
InChI=1S/C15H25N2.C7H8O3S/c1-3-17(4-2)13-8-11-16(12-14-17)15-9-6-5-7-10-15;1-6-2-4-7(5-3-6)11(8,9)10/h5-7,9-10H,3-4,8,11-14H2,1-2H3;2-5H,1H3,(H,8,9,10)/q+1;/p-1

HIDE SMILES / InChI

Molecular Formula C7H7O3S
Molecular Weight 171.194
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C15H25N2
Molecular Weight 233.3724
Charge 1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

1,1-DIETHYL-4-PHENYLHOMOPIPERAZINIUM (ASM-024), a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. ASM-024 is able to activate the α7 nAChR channel opening in the presence of the positive allosteric modulator (PNU-120596), indicating that ASM-024 behaves as a ‘silent agonist’ that places the receptor in a desensitized state. Compounds with similar properties have been shown to induce signal transduction pathways independently of ion channel activation. ASM-024 has demonstrated an antagonist effect on ACH-evoked activation at the M1, M2 and M3 muscarinic receptors expressed in Xenopus oocytes. A comprehensive nonclinical safety program was conducted with ASM-024 including pharmacokinetic and metabolism studies, safety pharmacology studies, toxicology and genotoxicity studies. In all, seven clinical studies were completed to evaluate the safety, tolerability and clinical activity of ASM-024. Three Phase I and four Phase II clinical trials were conducted on healthy subjects and patients with mild allergic asthma, stable moderate asthma and subjects with COPD. Altogether, ASM-024 has been safely administered to more than 200 subjects via the oral and inhalation delivery, i.e. nebulized solution and dry powder inhalation. However, the outcome of two phase II pilot studies in patients failed to demonstrate sufficient efficacy of ASM-024 in asthma and COPD. Thus, further work on ASM-024 on pulmonary diseases was stopped. In light of the findings that ASM‐024 blocks both nicotinic and muscarinic receptor activation, it is believed that ASM-024 will be a potent inhibitor of cell growth. These properties may have the potential to reduce the development or progression of tumors expressing these receptors. Based on a greater knowledge of the unique pharmacological mechanisms of action of ASM-024 developed at Asmacure, Odan is exploring the potential therapeutic role of ASM-024 in the treatment of selected oncology diseases. These studies include the in vitro anti-proliferative properties against a panel of various cancer cell lines and the in vivo anti-tumor activity in selected mouse models. Overall, the most significant inhibitory effect on in vitro cell proliferation was observed on the following cell lines: human lung adenocarcinoma, breast cancer, brain neuroblastoma, prostate adenocarcinoma and malignant melanoma. Preliminary data from a mouse model of lung carcinoma (Lewis Lung Cancer) using a slow infusion delivery method that ASM-024 treatment reduces the size and number of tumor nodules in the lung. In addition the potential therapeutic synergism between ASM-024 with commonly used chemotherapeutic agents will be investigated. Cisplatin and the taxanes (e.g. paclitaxel or Taxol) are commonly used chemotherapeutic agents, but their use is limited by their toxicity rates and innate or acquired resistance to these drugs. The concomitant effect of ASM-024 and cisplatin or Taxol on the proliferation of tumor cells will be assessed in vitro and potentially in in vivo mouse models. In the long term, Odan will consider to pursue the development of ASM-024 in a solution formulation administered intravenously (IV) in conjunction with the commonly-used cancer chemotherapeutic agents, for the growth inhibition and possibly regression of tumors in cancer patients.

Approval Year

PubMed

PubMed

TitleDatePubMed
Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.
2014
Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.
2015 Jul-Aug

Sample Use Guides

ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout.
Route of Administration: Respiratory
Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05).
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:09:52 GMT 2023
Edited
by admin
on Sat Dec 16 11:09:52 GMT 2023
Record UNII
R67KC9COEN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ASM-024
Common Name English
1H-1,4-DIAZEPINIUM, 1,1-DIETHYLHEXAHYDRO-4-PHENYL-, 4-METHYLBENZENESULFONATE (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
R67KC9COEN
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
PRIMARY
ChEMBL
CHEMBL3707249
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
PRIMARY
CAS
1624347-94-9
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
NO STRUCTURE GIVEN
PUBCHEM
117587641
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
ASM-024
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
PRIMARY Substance Name: ASM-024RN: 1609534-90-8UNII: R67KC9COENInChIKey: PXRYYARWCNIUKT-UHFFFAOYSA-M
CAS
1609534-90-8
Created by admin on Sat Dec 16 11:09:52 GMT 2023 , Edited by admin on Sat Dec 16 11:09:52 GMT 2023
PRIMARY
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ACTIVE MOIETY