myoseverin profile

Myoseverin is a potent and selective inhibitor of myosin light chain kinase (MLCK). MLCK is an enzyme that plays a crucial role in smooth muscle contraction by phosphorylating the regulatory light chain of myosin. Myoseverin inhibits MLCK by binding to the ATP-binding site of the enzyme. It has been shown to relax smooth muscle in various tissues, including the gastrointestinal tract, bladder, and airways. Myoseverin's high selectivity for MLCK makes it a potential therapeutic agent for conditions involving smooth muscle dysfunction, such as asthma, hypertension, and irritable bowel syndrome. Research on myoseverin is ongoing to explore its potential applications in these conditions. Myoseverin is a synthetic compound that has been synthesized using a variety of methods. Its effects are primarily attributed to its ability to inhibit MLCK, leading to smooth muscle relaxation. The importance of studying myoseverin lies in its potential as a therapeutic agent for a range of conditions related to smooth muscle dysfunction. Its selectivity for MLCK makes it a promising target for drug development in these areas.'

myoseverin: a micotubule-binding molecule with cellular effects; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	4273
CHEMBL ID	141689
SCHEMBL ID	13325947
MeSH ID	M0361815

Synonym
SMP2_000092
NCGC00165829-01
9-isopropyl-n2,n6-bis-(4-methoxybenzyl)-9h-purine-2,6-diamine
myoseverin
HSCI1_000041
CHEMBL141689
267402-71-1
2-n,6-n-bis[(4-methoxyphenyl)methyl]-9-propan-2-ylpurine-2,6-diamine
HMS2043N15
9h-purine-2,6-diamine, n,n'-bis((4-methoxyphenyl)methyl)-9-(1-methylethyl)-
SCHEMBL13325947
9-isopropyl-n2,n6-bis-(4-methoxy-benzyl)-9h-purine-2,6-diamine
M2373
9-isopropyl-2,6-bis(4-methoxybenzylamino)purine
AKOS027326433
bdbm50473494
J-016534
mfcd02683596
A12366
CS-W009672
9-isopropyl-n2,n6-bis(4-methoxybenzyl)-9h-purine-2,6-diamine
AS-56244
HY-W008956

Excerpt	Reference	Relevance
"Myoseverin treated cardiac myocytes showed disruptions of the striated Z-bands containing alpha-actinin and desmin and the localization of tropomyosin, titin and myosin on mature sarcomeric filaments."	( Myoseverin disrupts sarcomeric organization in myocytes: an effect independent of microtubule assembly inhibition. Bogoyevitch, MA; Gebski, BL; Grounds, MD; Ng, DC, 2008)	2.51

Protein Targets (7)

Potency Measurements

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASE	Homo sapiens (human)	Potency	44.6684	0.0032	45.4673	12,589.2998	AID2517
Chain A, TYROSYL-DNA PHOSPHODIESTERASE	Homo sapiens (human)	Potency	50.1187	0.0040	23.8416	100.0000	AID485290
Chain A, Ferritin light chain	Equus caballus (horse)	Potency	50.1187	5.6234	17.2929	31.6228	AID485281
nuclear receptor ROR-gamma isoform 1	Mus musculus (house mouse)	Potency	12.5893	0.0079	8.2332	1,122.0200	AID2551
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Tubulin beta-2B chain	Bos taurus (cattle)	IC50 (µMol)	8.0000	0.2500	1.8838	8.7000	AID214020
Similar to alpha-tubulin isoform 1	Bos taurus (cattle)	IC50 (µMol)	8.0000	0.2500	1.8779	8.7000	AID214020
Similar to alpha-tubulin isoform 1	Bos taurus (cattle)	IC50 (µMol)	8.0000	0.2500	1.8656	8.7000	AID214020
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (3)

Process	via Protein(s)	Taxonomy
microtubule-based process	Tubulin beta-2B chain	Bos taurus (cattle)
nervous system development	Tubulin beta-2B chain	Bos taurus (cattle)
positive regulation of axon guidance	Tubulin beta-2B chain	Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (3)

Process	via Protein(s)	Taxonomy
GTPase activity	Tubulin beta-2B chain	Bos taurus (cattle)
metal ion binding	Tubulin beta-2B chain	Bos taurus (cattle)
protein heterodimerization activity	Tubulin beta-2B chain	Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (1)

Process	via Protein(s)	Taxonomy
microtubule cytoskeleton	Tubulin beta-2B chain	Bos taurus (cattle)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (29)

Assay ID	Title	Year	Journal	Article
AID1673337	Induction of cellularization in human primary myotube assessed as alpha-tubulin level at 20 uM incubated for 72 hrs by Western blot analysis (Rvb = 0.674 No_unit)	2019	Bioorganic & medicinal chemistry, 07-01, Volume: 27, Issue:13	A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity.
AID353122	Cell cycle arrest in human SW480 cells assessed as accumulation at G2/M phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353121	Cell cycle arrest in human SW480 cells assessed as accumulation at S phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353115	Cell cycle arrest in human HCT116 cells assessed as accumulation at S phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353125	Antimitotic activity in human HeLa cells expressing GFP-tubulin assessed as induction of mitotic deffects by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID1518329	Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay	2019	European journal of medicinal chemistry, Dec-15, Volume: 184	Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer.
AID353129	Antimitotic activity in human HeLa cells expressing GFP-tubulin assessed as increase in aberration of mitotic spindle after 24 hrs by fluorescence microscopy	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID1518330	Antiproliferative activity against human A549 cells after 72 hrs by MTT assay	2019	European journal of medicinal chemistry, Dec-15, Volume: 184	Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer.
AID353112	Cytotoxicity against human SW48 cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353127	Antimitotic activity in human HeLa cells expressing GFP-tubulin assessed as aberration of mitotic spindle at 12 uM after 24 hrs by fluorescence microscopy	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353109	Cytotoxicity against human MES-SA cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID1673334	Induction of cellularization in human primary myotube assessed as beta-actin level at 20 uM incubated for 72 hrs by Western blot analysis (Rvb = 1.095 No_unit)	2019	Bioorganic & medicinal chemistry, 07-01, Volume: 27, Issue:13	A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity.
AID353108	Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353123	Inhibition of tubulin polymerization in bovine brain	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353126	Antimitotic activity in human HeLa cells expressing GFP-tubulin assessed as block of G2/M phase after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353114	Cell cycle arrest in human HCT116 cells assessed as accumulation at G1 phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353116	Cell cycle arrest in human HCT116 cells assessed as accumulation at G2/M phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353118	Cell cycle arrest in human SW48 cells assessed as accumulation at S phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353120	Cell cycle arrest in human SW480 cells assessed as accumulation at G1 phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353110	Cytotoxicity against human CEM cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID214020	Inhibition of tubulin polymerization using bovine brain tubulin	2001	Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26	Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors.
AID353130	Antimitotic activity in human HeLa cells expressing GFP-tubulin assessed as collapse of spindle microtubule at 12 uM by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID1424633	Inhibition of rhodamine-labeled purified porcine brain tubulin polymerization in presence of GTP incubated for 30 mins by epifluorescence microscopy	2017	European journal of medicinal chemistry, Dec-15, Volume: 142	1,3,5-Triazines: A promising scaffold for anticancer drugs development.
AID1518331	Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay	2019	European journal of medicinal chemistry, Dec-15, Volume: 184	Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer.
AID353117	Cell cycle arrest in human SW48 cells assessed as accumulation at G1 phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353111	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353119	Cell cycle arrest in human SW48 cells assessed as accumulation at G2/M phase at 30 uM after 24 hrs by flow cytometry	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID353113	Cytotoxicity against human SW480 cells after 72 hrs by MTT assay	2009	Bioorganic & medicinal chemistry, May-01, Volume: 17, Issue:9	Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives.
AID214561	Growth inhibition of human U937 cells	2001	Journal of medicinal chemistry, Dec-20, Volume: 44, Issue:26	Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	12 (75.00)	29.6817
2010's	4 (25.00)	24.3611
2020's	0 (0.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	3 (18.75%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	13 (81.25%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
chlorambucil Chlorambucil: A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed). chlorambucil : A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.	3.25	1	aromatic amine; monocarboxylic acid; nitrogen mustard; organochlorine compound; tertiary amino compound	alkylating agent; antineoplastic agent; carcinogenic agent; drug allergen; immunosuppressive agent
nocodazole [no description available]	2.02	1	aromatic ketone; benzimidazoles; carbamate ester; thiophenes	antimitotic; antineoplastic agent; microtubule-destabilising agent; tubulin modulator
reserpine Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.. reserpine : An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.	2.21	1	alkaloid ester; methyl ester; yohimban alkaloid	adrenergic uptake inhibitor; antihypertensive agent; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; first generation antipsychotic; plant metabolite; xenobiotic
paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).	2.21	1	taxane diterpenoid; tetracyclic diterpenoid	antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent
capecitabine Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.	2.21	1	carbamate ester; cytidines; organofluorine compound	antimetabolite; antineoplastic agent; prodrug
pyrazolo(3,4-d)pyrimidine [no description available]	2.03	1
2-(4-morpholinoanilino)-6-cyclohexylaminopurine 2-(4-morpholinoanilino)-6-cyclohexylaminopurine: structure in first source	3.12	1	morpholines; purines; secondary amino compound; tertiary amino compound	adenosine A3 receptor antagonist; antineoplastic agent; Aurora kinase inhibitor; cell dedifferentiation agent
6-bromoindirubin-3'-oxime 6-bromoindirubin-3'-oxime: structure in first source. 6-bromoindirubin-3'-oxime : A member of the class of biindoles that is indirubin substituted at position 6 by a bromo group and in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime.	2.21	1
fosbretabulin [no description available]	2.21	1	stilbenoid
zstk474 ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase.	3.25	1	benzimidazoles; morpholines; organofluorine compound; triamino-1,3,5-triazine	antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor

Condition	Relationship Strength	Studies
Benign Neoplasms [description not available]	3.06	1
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	3.06	1
Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.	2.21	1
Experimental Neoplasms [description not available]	2.21	1
Abnormalities, Drug-Induced Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.	2.03	1
Angiogenesis, Pathologic [description not available]	2.03	1

myoseverin

Description

Cross-References

Synonyms (23)

Research Excerpts

Treatment

Protein Targets (7)

Potency Measurements

Inhibition Measurements

Biological Processes (3)

Molecular Functions (3)

Ceullar Components (1)

Bioassays (29)

Research

Studies (16)

Market Indicators

Research Demand Index: 19.09

Study Types

myoseverin

Description

Cross-References

Synonyms (23)

Research Excerpts

Treatment

Protein Targets (7)

Potency Measurements

Inhibition Measurements

Biological Processes (3)

Molecular Functions (3)

Ceullar Components (1)

Bioassays (29)

Research

Studies (16)

Market Indicators

Research Demand Index: 19.09

Study Types

Related Drugs (10)

Related Conditions (6)