conophylline

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

conophylline: isolated from the leaves of Ervatamia microphylla; a ras function inhibitor; structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	9853848
MeSH ID	M0260358

Synonyms (10)

Synonym
cid 9853848
conophylline
142741-24-0
dimethyl 14,25-diethyl-24,33-dihydroxy-31,32-dimethoxy-12,22-dioxa-1,9,18,29-tetrazadodecacyclo[23.13.1.16,9.02,23.03,21.05,19.06,17.011,13.028,36.030,35.036,39.014,40]tetraconta-3,5(19),16,20,27,30,32,34-octaene-16,27-dicarboxylate
MS-31463
HY-N3619
CS-0023949
cophylline
B0005-166147
AKOS040740754

Research Excerpts

Overview

Conophylline (CNP) is a vinca alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It inhibits activation of pancreatic stellate cells.

Excerpt	Reference	Relevance
"Conophylline (CNP) is a vinca alkaloid extracted from the "	( Thermal Proteome Profiling Reveals Glutathione Peroxidase 4 as the Target of the Autophagy Inducer Conophylline. Hatanaka, T; Hosoi, T; Kakegawa, J; Ohtsuka, S; Ozawa, K; Yokoyama, M, 2021)	2.28
"Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants."	( Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models. Fukatsu, H; Koide, N; Kojima, I; Lin, Y; Nakade, Y; Simizu, S; Umezawa, K; Yoneda, M, 2018)	1.46
"Conophylline (CnP) is a vinca alkaloid purified from a tropical plant and inhibits activation of pancreatic stellate cells. "	( Conophylline suppresses hepatic stellate cells and attenuates thioacetamide-induced liver fibrosis in rats. Aoki, F; Hamano, K; Kojima, I; Kubo, N; Kuwano, H; Nagasawa, M; Saito, R; Takei, I; Umezawa, K, 2014)	3.29
"Conophylline (CnP) is a natural compound, which reproduces the effect of activin on β-cell differentiation and promotes β-cell neogenesis when administered in vivo."	( Conophylline suppresses pancreatic stellate cells and improves islet fibrosis in Goto-Kakizaki rats. Hara, A; Kimura, F; Kodera, T; Kojima, I; Saito, R; Takei, I; Tanaka, Y; Umezawa, K; Yamada, S; Yamamoto, Y, 2012)	2.54
"Conophylline is a vinca alkaloid extracted from the tropical plant Ervatamia microphylla and has been shown to induce differentiation of pancreatic AR42J cells. "	( Promotion of beta-cell differentiation by conophylline in fetal and neonatal rat pancreas. Kojima, I; Li, L; Ogata, T; Takei, I; Tanaka, Y; Umezawa, K; Yamada, S; Yamamoto, Y, 2004)	2.03

Actions

Conophylline did not inhibit the development of myocardial fibrosis in the presence of JNK activator anisomycin. It was found to suppress secretions of various inflammatory cytokines by pancreatic cancer-associated fibroblasts.

Excerpt	Reference	Relevance
"Conophylline did not inhibit the development of myocardial fibrosis in the presence of JNK activator anisomycin."	( Conophylline Suppresses Angiotensin II-Induced Myocardial Fibrosis In Vitro via the BMP4/JNK Pathway. Bao, YN; Du, XH; Lv, LY; Wang, YC; Zhang, SQ, 2021)	2.79
"Conophylline was found to suppress secretions of various inflammatory cytokines by pancreatic cancer-associated fibroblasts."	( Direct and Indirect Anticancer Activity of Plant-Derived Alkaloid Conophylline. Shirabe, K; Umezawa, K, 2021)	1.58
"Conophylline was found to activate autophagy in cultured neural cells."	( Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models. Fukatsu, H; Koide, N; Kojima, I; Lin, Y; Nakade, Y; Simizu, S; Umezawa, K; Yoneda, M, 2018)	1.46
"Conophylline did not inhibit nuclear translocation of Smad2."	( Suppression of TGF-beta signaling by conophylline via upregulation of c-Jun expression. Atsumi, S; Kowithayakornd, T; Koyano, T; Nagasawa, A; Umezawa, K, 2003)	1.31
"Conophylline did not increase expression of fibronectin but induced E-cadherin expression in K-ras-NIH3T3 cells."	( Inhibition of cellular chemotactic invasion by a vinca alkaloid, conophylline. Amino, N; Koyano, T; Ohse, T; Umezawa, K, )	1.09

Treatment

Conophylline significantly reduced the plasma glucose concentration and improved glucose tolerance in response to glucose loading.

Excerpt	Reference	Relevance
"Conophylline-treated cells were found to express insulin as measured at both mRNA and protein levels."	( Induction of insulin production in rat pancreatic acinar carcinoma cells by conophylline. Hiroki, A; Kam, TS; Kawakami, M; Kojima, I; Kowithayakorn, T; Koyano, T; Naka, H; Ogata, T; Pang, HS; Takei, I; Umezawa, K, 2003)	1.27
"Treatment with conophylline significantly reduced the plasma glucose concentration and improved glucose tolerance in response to glucose loading."	( Promotion of beta-cell differentiation by conophylline in fetal and neonatal rat pancreas. Kojima, I; Li, L; Ogata, T; Takei, I; Tanaka, Y; Umezawa, K; Yamada, S; Yamamoto, Y, 2004)	0.93

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (28)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	1 (3.57)	18.2507
2000's	10 (35.71)	29.6817
2010's	13 (46.43)	24.3611
2020's	4 (14.29)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 26.79

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	26.79 (24.57)
Research Supply Index	3.43 (2.92)
Research Growth Index	5.55 (4.65)
Search Engine Demand Index	29.35 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (26.79)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	3 (10.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	27 (90.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
niacinamide nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.	2.05	1	pyridine alkaloid; pyridinecarboxamide; vitamin B3	anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor
activins Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.	3.53	2
malondialdehyde Malondialdehyde: The dialdehyde of malonic acid.. malonaldehyde : A dialdehyde that is propane substituted by two oxo groups at the terminal carbon atoms respectively. A biomarker of oxidative damage to lipids caused by smoking, it exists in vivo mainly in the enol form.	2.15	1	dialdehyde	biomarker
deoxycytidine [no description available]	2.21	1	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
tiletamine hydrochloride Cyclohexanones: Cyclohexane ring substituted by one or more ketones in any position.. cyclohexanones : Any alicyclic ketone based on a cyclohexane skeleton and its substituted derivatives thereof.	3.18	1
gemcitabine gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.	2.21	1	organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; environmental contaminant; immunosuppressive agent; photosensitizing agent; prodrug; radiosensitizing agent; xenobiotic
angiotensin ii Giapreza: injectable form of angiotensin II used to increase blood pressure in adult patients with septic or other distributive shock. Ile(5)-angiotensin II : An angiotensin II that acts on the central nervous system (PDB entry: 1N9V).	7.31	1	amino acid zwitterion; angiotensin II	human metabolite
bromochloroacetic acid Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.. bromochloroacetic acid : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by bromine while a second is replaced by chlorine. A low-melting (27.5-31.5degreeC), hygroscopic crystalline solid, it can be formed during the disinfection (by chlorination) of water that contains bromide ions and organic matter, so can occur in drinking water as a byproduct of the disinfection process.	2.05	1	2-bromocarboxylic acid; monocarboxylic acid; organochlorine compound
thioacetamide Thioacetamide: A crystalline compound used as a laboratory reagent in place of HYDROGEN SULFIDE. It is a potent hepatocarcinogen.. thioacetamide : A thiocarboxamide consiting of acetamide having the oxygen replaced by sulfur.	7.1	1	thiocarboxamide	hepatotoxic agent
dehydroxymethylepoxyquinomicin dehydroxymethylepoxyquinomicin: an NF-kappaB inhibitor; structure in first source	3.18	1
transforming growth factor beta Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.	2.01	1

Condition	Relationship Strength	Studies
Hepatocellular Carcinoma [description not available]	7.31	1
Cancer of Liver [description not available]	2.31	1
Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.	2.31	1
Liver Neoplasms Tumors or cancer of the LIVER.	2.31	1
Endomyocardial Fibrosis A condition characterized by the thickening of the ventricular ENDOCARDIUM and subendocardium (MYOCARDIUM), seen mostly in children and young adults in the TROPICAL CLIMATE. The fibrous tissue extends from the apex toward and often involves the HEART VALVES causing restrictive blood flow into the respective ventricles (CARDIOMYOPATHY, RESTRICTIVE).	2.31	1
Experimental Neoplasms [description not available]	2.31	1
Fatty Liver, Nonalcoholic [description not available]	3.78	3
Liver Steatosis [description not available]	2.58	2
Innate Inflammatory Response [description not available]	2.15	1
Fatty Liver Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.	7.58	2
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	2.15	1
Non-alcoholic Fatty Liver Disease Fatty liver finding without excessive ALCOHOL CONSUMPTION.	8.78	3
Degenerative Diseases, Central Nervous System [description not available]	3.09	1
Cardiometabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY.	3.09	1
Diabetes Mellitus, Adult-Onset [description not available]	3.41	2
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	3.09	1
Cirrhosis [description not available]	4.18	3
Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.	3.41	2
Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.	9.18	3
Neurodegenerative Diseases Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.	3.09	1
Metabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.	8.09	1
Cancer of Pancreas [description not available]	2.47	2
Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	2.47	2
Autoimmune Diabetes [description not available]	3	1
Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.	3	1
Cirrhosis, Liver [description not available]	2.1	1
Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.	2.1	1
Akinetic-Rigid Variant of Huntington Disease [description not available]	2.11	1
Idiopathic Parkinson Disease [description not available]	2.11	1
Protein Aggregation, Pathological A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION; POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.	2.11	1
Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)	2.11	1
Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	2.11	1
Alloxan Diabetes [description not available]	2.73	3
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	2.05	1
Impaired Glucose Tolerance [description not available]	2.05	1
Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	2.05	1
Glucose Intolerance A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.	2.05	1
Leukemia, Lymphocytic, T Cell [description not available]	2.01	1
Leukemia, T-Cell A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.	2.01	1
Acinar Carcinoma [description not available]	7.01	1
Carcinoma, Acinar Cell A malignant tumor arising from secreting cells of a racemose gland, particularly the salivary glands. Racemose (Latin racemosus, full of clusters) refers, as does acinar (Latin acinus, grape), to small saclike dilatations in various glands. Acinar cell carcinomas are usually well differentiated and account for about 13% of the cancers arising in the parotid gland. Lymph node metastasis occurs in about 16% of cases. Local recurrences and distant metastases many years after treatment are common. This tumor appears in all age groups and is most common in women. (Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1240; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)	2.01	1
Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	2.02	1

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