Target type: biologicalprocess
Any semaphorin-plexin signaling pathway that is involved in axon guidance. [GOC:BHF, GOC:rl, GOC:TermGenie, PMID:22790009]
The semaphorin-plexin signaling pathway plays a crucial role in guiding axons to their appropriate targets during neuronal development. This intricate pathway involves a complex interplay of transmembrane receptors, intracellular signaling molecules, and extracellular cues. Semaphorins, a family of secreted or membrane-bound proteins, act as repulsive or attractive guidance cues for axons. They exert their effects by binding to plexins, a family of transmembrane receptors that initiate intracellular signaling cascades.
Upon semaphorin binding, plexins undergo conformational changes, activating downstream signaling pathways. The most prominent signaling pathway involves the recruitment of intracellular adaptor proteins, such as the GTPase activating protein (GAP) called p120GAP, which in turn inhibits the activity of the small GTPase Rac. Rac is a key regulator of cytoskeletal dynamics, and its inhibition by p120GAP leads to collapse of the growth cone, the dynamic structure at the tip of an axon that senses guidance cues. This collapse results in the repulsion of the axon away from the source of semaphorin.
However, the semaphorin-plexin signaling pathway is not solely repulsive. Certain semaphorins can also act as attractive guidance cues, promoting axon growth toward their source. This attractive signaling is mediated by different downstream pathways that involve the activation of other small GTPases, such as RhoA, or the recruitment of intracellular tyrosine kinases, such as Src. These alternative pathways can promote the extension of the growth cone and the formation of new filopodia, which are finger-like projections that explore the environment for guidance cues.
The semaphorin-plexin signaling pathway is highly regulated and involves a complex network of interactions with other signaling pathways, including those mediated by netrins, ephrins, and slits. This intricate interplay ensures precise axon guidance and the formation of functional neural circuits during development. It is also crucial for plasticity and rewiring of neuronal connections throughout life.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Endothelin-converting enzyme 1 | An endothelin-converting enzyme 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P42892] | Homo sapiens (human) |
| Endothelin-1 receptor | An endothelin-1 receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:P25101] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| thiorphan | Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms. | N-acyl-amino acid | |
| avapro | irbesartan : A biphenylyltetrazole that is an angiotensin II receptor antagonist used mainly for the treatment of hypertension. Irbesartan: A spiro compound, biphenyl and tetrazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION, and in the treatment of kidney disease. | azaspiro compound; biphenylyltetrazole | angiotensin receptor antagonist; antihypertensive agent; environmental contaminant; xenobiotic |
| mianserin | mianserin : A dibenzoazepine (specifically 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine) methyl-substituted on N-2. Closely related to (and now mostly superseded by) the tetracyclic antidepressant mirtazapinean, it is an atypical antidepressant used in the treatment of depression throughout Europe and elsewhere. Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. | dibenzoazepine | adrenergic uptake inhibitor; alpha-adrenergic antagonist; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; geroprotector; H1-receptor antagonist; histamine agonist; sedative; serotonergic antagonist |
| propranolol | propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3. Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. | naphthalenes; propanolamine; secondary amine | anti-arrhythmia drug; antihypertensive agent; anxiolytic drug; beta-adrenergic antagonist; environmental contaminant; human blood serum metabolite; vasodilator agent; xenobiotic |
| sulfathiazole | sulfathiazole : A 1,3-thiazole compound having a 4-aminobenzenesulfonamido group at the 2-position. Sulfathiazole: A sulfathiazole compound that is used as a short-acting anti-infective agent. It is no longer commonly used systemically due to its toxicity, but may still be applied topically in combination with other drugs for the treatment of vaginal and skin infections, and is still used in veterinary medicine. | 1,3-thiazoles; substituted aniline; sulfonamide; sulfonamide antibiotic | antiinfective agent; drug allergen; EC 2.5.1.15 (dihydropteroate synthase) inhibitor; environmental contaminant; xenobiotic |
| sulfisoxazole | sulfisoxazole : A sulfonamide antibacterial with an oxazole substituent. It has antibiotic activity against a wide range of gram-negative and gram-positive organisms. Sulfisoxazole: A short-acting sulfonamide antibacterial with activity against a wide range of gram- negative and gram-positive organisms. | isoxazoles; sulfonamide; sulfonamide antibiotic | antibacterial drug; drug allergen |
| captopril | captopril : A L-proline derivative in which L-proline is substituted on nitrogen with a (2S)-2-methyl-3-sulfanylpropanoyl group. It is used as an anti-hypertensive ACE inhibitor drug. Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin. | alkanethiol; L-proline derivative; N-acylpyrrolidine; pyrrolidinemonocarboxylic acid | antihypertensive agent; EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor |
| bosentan anhydrous | Bosentan: A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS. | primary alcohol; pyrimidines; sulfonamide | antihypertensive agent; endothelin receptor antagonist |
| 1h-indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1s,2r,3s)- | 1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-: an ET(A) and ET(B) endothelin receptor antagonist; structure in first source | ||
| ro 46-2005 | Ro 46-2005: an orally active non-peptide antagonist of endothelin receptors; structure given in first source | ||
| pd 142893 | PD 142893: functional antagonist of endothelin-stimulated vasoconstriction | ||
| 5-(dimethylamino)-n-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide | 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide: structure in first source; endothelin receptor antagonist | naphthalenes; sulfonic acid derivative | |
| tak 044 | TAK 044: endothelin receptor antagonist | ||
| endothelin (16-21) | endothelin (16-21): C-terminal hexapeptide of endothelin; amino acid seq. given in first source | peptide | |
| 2-(4-morpholinyl)-4h-1-benzopyran-4-one | 2-(4-morpholinyl)-4H-1-benzopyran-4-one: an aminochromone; exhibits both antiproliferative and antichemotactic activity in vitro | ||
| cgs 26303 | CGS 26303: a potent non-peptidic inhibitor of neutral endopeptidase capable of protecting atrial natriuretic peptide from enzymatic degradation; structure given in first source | ||
| tezosentan | tezosentan: structure in first source | ||
| bms 207940 | N-((2'-(((4,5-dimethyl-3-isoxazolyl)amino)sulfonyl)-4-(2-oxazolyl)(1,1'-biphenyl)-2-yl)methyl)-N,3,3-trimethylbutanamide: an ET(A) receptor antagonist; structure in first source | ||
| atrasentan | Atrasentan: A pyrrolidine and benzodioxole derivative that acts a RECEPTOR, ENDOTHELIN A antagonist. It has therapeutic potential as an antineoplastic agent and for the treatment of DIABETIC NEPHROPATHIES. | pyrrolidines | |
| lu 135252 | |||
| enrasentan | enrasentan : A member of the class of indanes that is 2,3-dihydro-1H-indene which is substituted by a 1,3-benzodioxol-5-yl group, carboxy group, 2-(2-hydroxyethoxy)-4-methoxyphenyl group and a propoxy group at positions 1S, 2R, 3S and 5, respectively. It is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. The drug was being developed by GSK for the treatment of congestive heart failure and pulmonary hypertension (clinical trials discontinued). enrasentan: decreases ischemic brain injury; an endothelin A and B receptor antagonist; structure in first source | aromatic ether; benzodioxoles; indanes; monocarboxylic acid; monomethoxybenzene; primary alcohol | antihypertensive agent; endothelin receptor antagonist |
| 2-[(4,6-dimethyl-2-pyrimidinyl)oxy]-3-methoxy-3,3-diphenylpropanoic acid | diarylmethane | ||
| tbc-11251 | sitaxsentan: endothelin A receptor antagonist; structure in first source | benzodioxoles | |
| bq 123 | cyclo(Trp-Asp-Pro-Val-Leu): derived from the modification of a natural lead of BE-18257B, an endothelin A receptor antagonist; has neuroprotective activity; amino acid sequence given in first source | cyclic peptide | |
| phosphoramidon | phosphoramidon : A dipeptide isolated from the cultures of Streptomyces tanashiensis. phosphoramidon: a membrane metallo-endopeptidase & endothelin-converting enzyme inhibitor; thermolysin inhibitor from culture filtrate of Streptomyces tanashiensis; structure | deoxyaldohexose phosphate; dipeptide | bacterial metabolite; EC 3.4.24.11 (neprilysin) inhibitor; EC 3.4.24.71 (endothelin-converting enzyme 1) inhibitor |
| a 192621 | A 192621: ET(B) receptor antagonist | ||
| benzyloxycarbonyl-phe-ala-fluormethylketone | cathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1). | ||
| irl 2500 | IRL 2500: Endothelin-B receptor antagonist; structure in first source | ||
| ro 46-8443 | Ro 46-8443: a non-peptide endothelin ET(B) receptor selective antagonist; structure given in first source | ||
| sulindac sulfone | sulindac sulfone : A sulfone metabolite of sulindac that inhibits cell growth by inducing apoptosis independently of cyclooxygenase inhibition. It inhibits the development and induces regression of premalignant adenomatous polyps. Lipoxygenase and Cox-2 inhibitor. sulindac sulfone: inhibits K-ras-dependent cyclooxygenase-2; sulfated analog of indomethacin;; CP248 is an antineoplastic agent that fosters microtubule depolymerization; structure in first source | monocarboxylic acid; organofluorine compound; sulfone | apoptosis inducer; cyclooxygenase 2 inhibitor; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor |
| ro 47-8634 | Ro 47-8634: structure in first source | ||
| clazosentan | clazosentan: endothelin A receptor antagonist used for cerebral vasospasm; structure in first source; | ||
| lu 224332 | felotaxel: an antineoplastic agent; structure in first source | ||
| lu 208075 | ambrisentan: an ET(A) receptor antagonist and antihypertensive agent; studied for use in pulmonary arterial hypertension | diarylmethane | |
| bms 193884 | |||
| cgs 35066 | CGS 35066: an endothelin-converting enzyme-1 inhibitor; structure in first source | ||
| ci 1020 | |||
| lu 302872 | LU 224332: endothelin-A/B receptor antagonist | ||
| bms 248360 | |||
| zibotentan | ZD4054: a potent endothelin receptor A antagonist that inhibits ovarian carcinoma cell proliferation | phenylpyridine | |
| avosentan | Avosentan: structure in first source | ||
| 4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1-butyl)-piperidine hydrogen chloride | |||
| s 3304 | S 3304: structure in first source | ||
| naluzotan | naluzotan: an antidepressant and anti-anxiety agent; structure in first source | ||
| macitentan | aromatic ether; organobromine compound; pyrimidines; ring assembly; sulfamides | antihypertensive agent; endothelin receptor antagonist; orphan drug | |
| a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source | ||
| endothelin-1 | Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63) | ||
| pd 156707 | |||
| act-132577 | ACT-132577 : A member of the class of sulfamides in which one of the amino groups of sulfonamide is substituted by a 5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl group. An active metabolite of macitentan (obtained by oxidative depropylation), an orphan drug used for the treatment of pulmonary arterial hypertension. aprocitentan: a macitentan metabolite | aromatic ether; organobromine compound; pyrimidines; sulfamides | antihypertensive agent; drug metabolite; endothelin receptor antagonist; xenobiotic metabolite |
| endothelins | |||
| nitd 609 | NITD 609: an antimalarial and coccidiostat; structure in first source |