Leteprinim (AIT 082 acid) is an hypoxanthine derivative that stimulates in vitro neurite outgrowth and the production of adenosine and neurotrophins from astrocytes.

Brexpiprazole HCl (OPC 34712 dihydrochloride) is a new antipsychotic drug.

2,6,4'-Trihydroxy-4-methoxybenzophenone shows weak inhibitory activity of testosterone 5alpha-reductase, it also shows significant inhibition of pancreatic lipase activity. 2,6,4'-Trihydroxy-4-methoxybenzophenone has neurotrophic activity, it induced neurite outgrowth in PC-12 cells at concentration of 50 microg/ml. 2,6,4′-Trihydroxy-4-methoxybenzophenone exhibits low cytotoxic effect against HeLa and 3T3 cell lines with IC50 values of 132 ug/ml and 158 ug/ml, repectively. It also shows antioxidant activity on DPPH with IC50 of 10.57 ug/mL.

Scabronine M, a novel inhibitor, impedes NGF-induced neurite outgrowth from PC12 cells.

PA22-2, an active biological peptide featuring the IKVAV sequence from the laminin A-chain fragment, is derived from mouse laminin alpha1 amino acid residues 2110-2127. Substrates composed of PA22-2 have been shown to facilitate neurite outgrowth.

NG-012, a nerve growth factor (NGF) potentiator, was isolated from the culture broth of Penicillium verruculosum F-4542. It enhances neurite outgrowth as induced by NGF in the rat pheochromocytoma cell line (PC12) [1].

PA22-2 (free acid) (Cys-Laminin A chain 2091-2108), a peptide, promotes neurite outgrowth and facilitates the formation of neuron-like processes. It is utilized in the culturing of human adenoid cystic carcinoma cells and the development of peptide-functionalized supported phospholipid bilayers [1] [2] [3].

Kissoone C (compound 3), a sesquiterpene with a three-membered ring structure, has been isolated from valerian root. This compound has been found to promote nerve growth factor (NGF)-mediated neurite outgrowth in PC12D cells [1].

Peptide fragment corresponding to residues 1 - 40 of Nogo-66, the domain of the myelin protein Nogo that inhibits axonal outgrowth. Acts as a competitive antagonist at the Nogo-66 receptor (NgR); blocks Nogo-66- and CNS myelin-induced inhibition of axonal

Lactacystin is an antibiotic Streptomyces spp. the metabolite and is an effective and selective proteasome inhibitor (IC50: 4.8 μM for 20S proteasome). Lactacystin inhibits cell growth and induces neurite outgrowth and also inhibits the lysosomal enzyme cathepsin A.

Olodanrigan (EMA401), a highly selective AT2R antagonist, inhibition of augmented AngII/AT2R induced p38 and p42/p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons. EMA401 blocks p38, p42/p44 mitogen-activated protein kinase (MAPK) activation, neurite outgrowth in adult rat DRG neurons, and sensitization of adult rat and human DRG neurons induced by AngII. It inhibits capsaicin responses in cultured hDRG neurons.

Ozanezumab (GSK1223249) is a monoclonal antibody targeting Nogo-A (neurite outgrowth inhibitor A). It is utilized in research related to amyotrophic lateral sclerosis (ALS) and multiple sclerosis [1].

Erinacine U, a cyanogen diterpene extracted from Hericium erinaceus, exhibits neurotrophic properties and significantly enhances neurite outgrowth in PC12 cells [1].

(-)-Neuchromenin is an inducer of neurite outgrowth of PC12 cells at concentration of 2.5-10 ug/ml.

4,10-Aromadendranediol exhibits neurite outgrowth-inducing activity in neurons via activation of the ERK signaling pathway, which may be beneficial to the treatment of brain diseases.

1-β-D-Glucosylsphingadienine is a glucosylsphingosine, which are deacetylated lysolipid derivatives of glucosylcerebrosides . They are formed when sphingosines undergo glucosidation by UDP-glucose. Glucosylsphingosines completely reduce neurite outgrowth and induce death of LA-N-2 cells at concentrations of 10 and 50 μM, respectively. They also decrease the activity of glucocerebrosidase in LA-N-2 cells in a dose-dependent manner. Glucosylsphingosine levels are elevated in patients with Gaucher's disease, both in the spleen (in types 1, 2, and 3) and brain (type 2 and 3); thus, glucosylsphingosine has been used as a key biomarker of the disease. This product contains 1-β-D-glucosylsphingadienine isolated from plants.

Isodunnianol exhibits anti-AChE activity with an IC50 value of 13.0 uM; it also exhibits neurite outgrowth-promoting activity at the concentration ranging from 0.1 to 10 uM in the primary cultured rat cortical neurons. Isodunnianol, dunnianol, and Macrant

Amisulpride is an antagonist of 5-HT7 receptor and dopamine D2 and D3 receptors. It modulates beta 2- arresting signaling and increases neurite outgrowth.

14-Norpseurotin A shows good antileishmanial and moderate anticancer activities. It also displays significant antimicrobial activities against Escherichia coli, Bacillus subtilis, and Micrococcus lysoleikticus with MICs of 3.74, 14.97, and 7.49 microM , r

Cyclo(L-Phe-L-Val) is a metabolite of the sponge bacterium Pseudoalteromonas sp. NJ6-3-1 that can autoinduce production of antibacterial substances active against S. aureus when co-cultured at a low cell density. It induces neurite outgrowth and branching of chick cortical neurons in vitro when used at concentrations of 16 and 32 μM. It increases phosphorylation of the PI3K substrate Akt, and neurite outgrowth induced by cyclo(L-Phe-L-Val) can be blocked by the PI3K inhibitor LY294002 . Cyclo(L-Phe-L-Val) enhances axon sprouting of calcitonin gene-related protein positive (CGRP+) primary afferents in the spinal cord following crush injury and of serotonin neurons in uninjured spinal cord. Cyclo(L-Phe-L-Val) is also a bitter taste component of cocoa and roasted coffee.

Cerevisterol is a cytotoxic steroid, can inhibit the activity of DNA polymerase alpha. It can stimulate NGF-mediated neurite outgrowth on PC12 cells.

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50= 0.025 μM). HDAC6-IN-5 inhibits Aβ 1-42 self-aggregation and AChE, with IC 50s of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

Insulin-like Growth Factor II (IGF-2), the primary somatomedin in human serum, exerts both permissive and direct influences on neurite outgrowth and significantly improves the survival of sympathetic and sensory neurons [1] [2].

HDAC6-IN-6 (compound 6a) is a potent inhibitor of HDAC6 that can penetrate BBB with an IC50 value of 0.025 μM. HDAC6-IN-6 has potent inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM. HDAC6-IN-6 can enhance the outgrowth of neurite without significant neurotoxicity [1].

Gentiside B is a potent inducer of neurite outgrowth on PC12 cells, it shows a significant neuritogenic activity at 30 microM against PC12 cells that is comparable to that seen for the best nerve growth factor (NGF) concentration of 40 ng/mL.

H-Ile-Lys-Val-Ala-Val-OH, a significant active site within laminin-1, enhances cell adhesion, neurite outgrowth, and tumor growth. It also encourages the growth and proliferation of BMMSC populations through the activation of MAPK/ERK1/2 and PI3K/Akt signaling pathways [1] [2].

1. Notoginsenosides Fa and R4 show significant neurite outgrowth enhancing activities in human neuroblastoma SK-N-SH cells.

1. Negletein (7-O-Methylbaicalein) has anti-inflammatory and immunomodulatory activities via inhibition of TNF-α, iNOS and IL-1β. 2. Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. 3. Negletein shows a comparable redox-active potential, and it (50 μM, 4 h) can activate Nrf2. 4. Negletein shows significant antimicrobial activity. 5. Negletein has anti-hypoxia activity, it can significantly prolong the survival time of hypoxic mice.6. Negletein has anti- Alzheimer's disease activity, it inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. 7. Negletein (IC50: 3.89 +/- 0.39 microM) exhibits potent inhibitory activity against nuclear factor of activated T cells (NFAT) transcription factor.

Acetylcarnitine arginyl amide is able to stimulate neurite outgrowth in a manner similar to that elicited by nerve growth factor (NGF). Neurite induction by this molecule requires de novo mRNA synthesis and is independent of the action of several common t

Talaumidin is a natural neurotrophic agent which promotes neurite outgrowth from neurons through the PI3K/Akt pathway.

(-)-L-threo-PDMP is an enhancer of ganglioside biosynthesis. The (-)-L-threo-PDMP (1S,2S) isomer is the active stimulatory component of DL-threo-PDMP in contrast to (+)-D-threo-PDMP , which is an inhibitor of glucosylceramide synthetase. (-)-L-threo-PDMP upregulates GM3, GD3, and GQ1b synthase levels, which are glycosyltransferases involved in ganglioside biosynthesis, and increases ganglioside levels in cells. It increases neurite outgrowth and synapse formation in vitro and improves retention of a long-term memory learned prior to forebrain ischemia in rats when administered following ischemia at a dose of 40 mg/kg per day.

RC-33 HCl is a selective and metabolically stable σ1 receptor agonist potentiating NGF-induced neurite outgrowth.

Broussonins A and B, new phytoalexins from diseased paper mulberry. Broussonin B can induce neurite outgrowth in PC-12 cells at concentration of 50 microg/ml, and show moderate inhibitory activities against a chymotrypsin-like activity of the proteasome.B

Eudesmin shows antiinflammatory, neuritogenic, anticonvulsant and sedative effects, the mechanism of eudesmin may be related to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the in brain.50 microM (+)-eudesmin can induce neurite outgrowth and enhance nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells by stimulating up-stream MAPK, PKC and PKA pathways.

Brexpiprazole (OPC-34712) is a partial agonist of human 5-hydroxytryptamine (5-HT) 5-HT1A and dopamine D2 receptors.

TAT-NEP1-40 acetate, a potential therapeutic for axonal regeneration and functional recovery post-stroke, safeguards PC12 cells from oxygen and glucose deprivation (OGD) and encourages neurite outgrowth. This compound also affords cerebral protection against ischemia/reperfusion injury by hindering neuronal apoptosis and can be effectively administered into rat brains [1] [2].

TAT-NEP1-40 TFA, a blood-brain barrier-permeable peptide, safeguards PC12 cells against oxygen and glucose deprivation (OGD) and fosters neurite outgrowth. Additionally, it enhances neurological outcomes post-ischemia by curtailing apoptosis in ischemic cerebral tissues. This compound has utility in investigating central nervous system (CNS) injuries, encompassing axonal regeneration and functional recuperation following a stroke [1].

Lalioside is a potent accelerator of neurite outgrowth.

1. Nardosinone has inhibitory effect on Ang II-induced hypertrophy in H9c2 cells, might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways. 2. Nardosinone could protect against the neuronal injury exposed to OGD, which may be relevant to the

Gentiside J is a potent inducer of neurite outgrowth on PC12 cells.

CITFA, a GPER agonist, enhances neurite outgrowth in rat embryonic (E18) hippocampal neurons [1].

Galgravin has anti-inflammatory, and neuroprotective effects, it can promote neuronal survival and neurite outgrowth, protect hippocampal neurons against amyloid beta peptide (Abeta25-35)-induced cytotoxicity, and protect against neuronal death from 1-met

Deoxyandrographolide (14-deoxyandrographolide) potentiates NGF-induced neurite outgrowth. Deoxyandrographolide suppresses the production of proinflammatory mediators TNF-α and IL-6.

TAT-NEP1-40, a blood-brain barrier (BBB) permeable peptide, confers protection to PC12 cells against oxygen and glucose deprivation (OGD) while promoting neurite outgrowth. Furthermore, it enhances neurologic outcomes post-ischemia by mitigating apoptosis in affected cerebral regions. This compound holds potential for central nervous system (CNS) injury research, including studies on axonal regeneration and post-stroke functional recovery [1].

Ganglioside sialidase (AuSialidase S), an endogenous metabolite, plays a critical role in neuronal differentiation, specifically in neurite outgrowth [1].

ACAF4 is a neurotrophic agent which significantly increases survival in PC12 neuronal cells and enhances the effect of nerve growth factor (NGF). ACAF4 induces neurite outgrowth, and modulates ERK1/2 and AKT signaling pathways.

B355252 protects against cell death caused by glutamate-evoked oxidative stress. B355252 shows neuroprotective effect, potentiating nerve growth factor (NGF)-induced neurite outgrowth.

(2R,3S)-Dihydrodehydroconiferyl alcohol can induce neurite outgrowth and enhance NGF-induced neurite outgrowth from PC12 cells by amplifying up-stream steps such as MAPK and PKC.

Secologanin dimethyl acetal induces significant neurite outgrowth.

Picroside I (6'-Cinnamoylcatalpol), a hepatoprotective agent, is reported to be antimicrobial and used against hepatitis B. It has antioxidant, and anti-inflammatory activities, it may be the valuable anti-invasive drug candidates for cancer therapy by suppressing Collagenases and Gelatinases. Picroside I can enhance basic fibroblast growth factor(bFGF)-, staurosporine- or dbc-mitogen-activated protein (MAP)-induced neurite outgrowth from PC12D cells.