https://www.medchemexpress.com/Pathways/Anti-infection.html2026-06-05daily https://www.medchemexpress.com/Pathways/Antibody-drug%20Conjugate_ADC%20Related.html2026-06-05daily https://www.medchemexpress.com/Pathways/Apoptosis.html2026-06-05daily https://s3.medchemexpress.com/pathway/MCE-Apoptosis-Signaling-Pathway.pngUpon binding to their cognate ligand, death receptors such as Fas and TRAILR can activate initiator Caspases (Pro-caspase 8 and Pro-caspase 10) through dimerization mediated by adaptor proteins such as FADD and TRADD. Active Caspase 8 and Caspase 10 then cleave and activate the effector Caspase 3, 6 and 7, leading to apoptosis. ROS/DNA damage and ER stress trigger Caspase 2 activation. Active Caspase 2 cleaves and activates Caspase 3 and initiates apoptosis directly. Caspase 2, 8 and 10 can also cleave Bid, stimulate mitochondrial outer membrane permeabilization (MOMP) and initiate the intrinsic apoptotic pathway. Following MOMP, mitochondrial intermembrane space proteins such as Smac and Cytochrome C are released into the cytosol. Cytochrome C interacts with Apaf-1, triggering apoptosome assembly, which activates Caspase 9. Active Caspase 9, in turn, activates Caspase 3, 6 and 7, leading to apoptosis. Mitochondrial release of Smac facilitates apoptosis by blocking the inhibitor of apoptosis (IAP) proteins. Following the binding of TNF to TNFR1, TNFR1 binds to TRADD, which recruits RIPK1, TRAF2/5 and cIAP1/2 to form TNFR1 signaling complex I. Formation of the complex IIa and complex IIb is initiated either by RIPK1 deubiquitylation mediated by CYLD or by RIPK1 non-ubiquitylation due to depletion of cIAPs. The Pro-caspase 8 homodimer in complex IIa and complex IIb generates active Caspase 8. This active Caspase 8 in the cytosol then carries out cleavage reactions to activate downstream executioner caspases and thus induce classical apoptosis[1][2]. Reference:[1]. Thomas C, et al. Caspases in retinal ganglion cell death and axon regeneration. Cell Death Discovery volume 3, Article number: 17032 (2017).[2]. Brenner D, et al. Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol. 2015 Jun;15(6):362-74.Apoptosis Signaling Pathway | MedChemExpresshttps://www.medchemexpress.com https://www.medchemexpress.com/Pathways/Autophagy.html2026-06-05daily https://s3.medchemexpress.com/pathway/MCE-Autophagy-Signaling-Pathway.pngAutophagy Signaling Pathway | MedChemExpresshttps://www.medchemexpress.com https://www.medchemexpress.com/Pathways/Cell%20Cycle_DNA%20Damage.html2026-06-05daily https://www.medchemexpress.com/Pathways/Cytoskeleton.html2026-06-05daily https://www.medchemexpress.com/Pathways/Epigenetics.html2026-06-05daily https://www.medchemexpress.com/Pathways/GPCR_G%20protein.html2026-06-05daily https://www.medchemexpress.com/Pathways/Immunology_Inflammation.html2026-06-05daily https://www.medchemexpress.com/Pathways/JAK_STAT%20Signaling.html2026-06-05daily https://www.medchemexpress.com/Pathways/MAPK_ERK%20Pathway.html2026-06-05daily https://www.medchemexpress.com/Pathways/Membrane%20Transporter_Ion%20Channel.html2026-06-05daily https://www.medchemexpress.com/Pathways/Metabolic%20Enzyme_Protease.html2026-06-05daily https://www.medchemexpress.com/Pathways/Neuronal%20Signaling.html2026-06-05daily https://www.medchemexpress.com/Pathways/NF-κB.html2026-06-05daily https://s3.medchemexpress.com/pathway/MCE-NF-kB-Signaling-Pathway.pngNF-κB transcription factors are critical regulators of immunity, stress responses, apoptosis and differentiation. In mammals, there are five members of the transcription factor NF-κB family: RELA (p65), RELB and c-REL, and the precursor proteins NF-κB1 (p105) and NF-κB2 (p100), which are processed into p50 and p52, respectively. NF-κB transcription factors bind as dimers to κB sites in promoters and enhancers of a variety of genes and induce or repress transcription. NF-κB activation occurs via two major signaling pathways: the canonical and the non-canonical NF-κB signaling pathways[1]. The canonical NF-κB pathway is triggered by signals from a large variety of immune receptors, such as TNFR, TLR, and IL-1R, which activate TAK1. TAK1 then activates IκB kinase (IKK) complex, composed of catalytic (IKKα and IKKβ) and regulatory (NEMO) subunits, via phosphorylation of IKKβ. Upon stimulation, the IKK complex, largely through IKKβ, phosphorylates members of the inhibitor of κB (IκB) family, such as IκBα and the IκB-like molecule p105, which sequester NF-κB members in the cytoplasm. IκBα associates with dimers of p50 and members of the REL family (RELA or c-REL), whereas p105 associates with p50 or REL (RELA or c-REL). Upon phosphorylation by IKK, IκBα and p105 are degradated in the proteasome, resulting in the nuclear translocation of canonical NF-κB family members, which bind to specific DNA elements, in the form of various dimeric complexes, including RELA-p50, c-REL-p50, and p50-p50. Atypical, IKK-independent pathways of NF-κB induction also provide mechanisms to integrate parallel signaling pathways to increase NF-κB activity, such as hypoxia, UV and genotoxic stress. The non-canonical NF-κB pathway is induced by certain TNF superfamily members, such as CD40L, BAFF and lymphotoxin-β (LT-β), which stimulates the recruitment of TRAF2, TRAF3, cIAP1/2 to the receptor complex. Activated cIAP mediates K48 ubiquitylation and proteasomal degradation of TRAF3, resulting in stabilization and accumulation of the NFκB-inducing kinase (NIK). NIK phosphorylates and activates IKKα, which in turn phosphorylates p100, triggering p100 processing, and leading to the generation of p52 and the nuclear translocation of p52 and RELB[2][3]. Reference:[1]. Oeckinghaus A, et al. The NF-kappaB family of transcription factors and its regulation.Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034. [2]. Taniguchi K, et al. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018 May;18(5):309-324.[3]. Perkins ND,et al. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007 Jan;8(1):49-62.NF-κB Signaling Pathway | MedChemExpresshttps://www.medchemexpress.com https://www.medchemexpress.com/Pathways/PI3K_Akt_mTOR.html2026-06-05daily https://s3.medchemexpress.com/pathway/MCE-PI3K-Signaling-Pathway.pngPhosphatidylinositol 3 kinases (PI3Ks) are a family of lipid kinases that integrate signals from growth factors, cytokines and other environmental cues, translating them into intracellular signals that regulate multiple signaling pathways. These pathways control many physiological functions and cellular processes, which include cell proliferation, growth, survival, motility and metabolism[1]. In the absence of activating signals, p85 interacts with p110 and inhibits p110 kinase activity. Following receptor tyrosine kinase (RTK) or G protein-coupled receptor (GPCR) activation, class I PI3Ks are recruited to the plasma membrane, where p85 inhibition of p110 is relieved and p110 phosphorylates PIP2 to generate PIP3. The activated insulin receptor recruits intracellular adaptor protein IRS1. Phosphorylation of IRS proteins on tyrosine residues by the insulin receptor initiates the recruitment and activation of PI3K. PIP3 acts as a second messenger which promotes the phosphorylation of Akt at Thr308 by PDK-1. RTK activation can also trigger Ras-Raf-MEK-ERK pathway. Activated Akt, ERK and RSK phosphorylate TSC2 at multiple sites to inhibit TSC1-TSC2-TBC1D7, which is the TSC complex that acts as a GTPase-activating protein (GAP) for the small GTPase RHEB. During inhibition of the TSC complex, GTP-loaded RHEB binds the mTOR catalytic domain to activate mTORC1. Glycogen synthase kinase 3β (GSK-3β) activates the TSC complex by phosphorylating TSC2 at Ser1379 and Ser1383. Phosphorylation of these two residues requires priming by AMPK-dependent phosphorylation of Ser1387. Wnt signaling inhibits GSK-3β and the TSC complex, and thus activates mTORC1. mTORC2 is activated by Wnt in a manner dependent on the small GTPase RAC1. Akt activation contributes to diverse cellular activities which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration. Important downstream targets of Akt are GSK-3, FOXOs, BAD, AS160, eNOS, and mTOR. mTORC1 negatively regulates autophagy through multiple inputs, including inhibitory phosphorylation of ULK1, and promotes protein synthesis through activation of the translation initiation promoter S6K and through inhibition of the inhibitory mRNA cap binding 4E-BP1[1][2][3]. PI3Kδ is a heterodimeric enzyme, typically composed of a p85α regulatory subunit and a p110δ catalytic subunit. In T cells, the TCR, the costimulatory receptor ICOS and the IL-2R can activate PI3Kδ. In B cells, PI3Kδ is activated upon crosslinking of the B cell receptor (BCR). The BCR co-opts the co-receptor CD19 or the adaptor B cell associated protein (BCAP), both of which have YXXM motifs to which the p85α SH2 domains can bind. In lumphocytes, BTK and ITK contribute to the activation of PLCγ and promotes the generation of DAG and the influx of Ca2+, which in turn activate PKC and the CARMA1-, BCL 10- and MALT1 containing (CBM) complex. The resulting NF-κB inhibitor kinase (IKK) activation leads to the phosphorylation and the degradation of IκB, and to the nuclear accumulation of the p50-p65 NF-κB heterodimer. MyD88 is an adapter protein that mediates signal transduction for most TLRs and leads to activation of PI3K[4]. Reference:[1]. Thorpe LM, et al. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting.Nat Rev Cancer. 2015 Jan;15(1):7-24. [2]. Vanhaesebroeck B, et al. PI3K signalling: the path to discovery and understanding.Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):195-203. [3]. Fruman DA, et al. The PI3K Pathway in Human Disease.Cell. 2017 Aug 10;170(4):605-635.[4]. Lucas CL, et al. PI3Kδ and primary immunodeficiencies.Nat Rev Immunol. 2016 Nov;16(11):702-714. PI3K/Akt/mTOR Signaling Pathway | MedChemExpresshttps://www.medchemexpress.com https://www.medchemexpress.com/Pathways/PROTAC.html2026-06-05daily https://www.medchemexpress.com/Pathways/Protein%20Tyrosine%20Kinase_RTK.html2026-06-05daily https://www.medchemexpress.com/Pathways/Stem%20Cells_Wnt.html2026-06-05daily https://www.medchemexpress.com/Pathways/TGF-beta_Smad.html2026-06-05daily https://www.medchemexpress.com/Pathways/Vitamin%20D%20Related.html2026-06-05daily https://www.medchemexpress.com/Pathways/Others.html2026-06-05daily