Autoimmune Disease Series--

Ulcerative Colitis

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory intestinal disease primarily affecting the colon and rectum. It is a subtype of inflammatory bowel disease (IBD). Its etiology is closely associated with genetic susceptibility, abnormal immune system activation, intestinal dysbiosis, and environmental factors (e.g., smoking, diet). Patients present with persistent or recurrent symptoms such as diarrhea, mucopurulent bloody stools, abdominal pain, and tenesmus.

Current UC drug development is shifting from broad-spectrum anti-inflammatory agents to targeted therapies. Biologics (e.g., IL-23, TL1A inhibitors) and precision small molecules (e.g., S1PR1-biased agonists) are emerging as frontier directions. Additionally, traditional Chinese medicine (TCM)-based multi-target regulation and novel technologies (nanomedicine, epigenetic interventions) offer new strategies to overcome therapeutic bottlenecks:

► Biologics

• IL-23/IL-12 Pathway: Xinda Biotech’s Picankibart (IL-23p19 mAb) demonstrates excellent efficacy and safety in Phase II trials, marking China’s first IL-23-targeted UC therapy. Merck’s MK-7240 (TL1A inhibitor) significantly improved endoscopic scores in Phase II trials, achieving a 26.5% clinical remission rate at 12 weeks, and has entered Phase III.
• Integrin Targets: Vedolizumab, which blocks lymphocyte migration to the gut mucosa, outperforms adalimumab in head-to-head comparisons. Etrolizumab (same target) failed due to inconsistent efficacy.
• Chemokines/Inflammatory Cytokines: Mendelian randomization studies suggest CXCL5 reduces IBD risk, while CXCL9 increases it, highlighting their therapeutic potential ^[1]. Genetically predicted lower CD40 levels correlate with reduced IBD risk, likely via immune cell interaction modulation.

► Small Molecule Drugs

• S1P Receptors: SAR247799 selectively activates S1PR1-G protein signaling, preserving endothelial barrier integrity with fewer off-target effects than non-selective modulators. Pfizer’s Etrasimod and approved Ozanimod show robust efficacy in refractory UC.
• JAK-STAT Pathway: JAK inhibitors (e.g., tofacitinib) alleviate UC symptoms by blocking inflammatory signaling but face limitations due to cardiovascular and infection risks.
• Purinergic Signaling: Researchers at China Pharmaceutical University identified P2Y14R inhibition as a novel target, reducing intestinal epithelial necroptosis via the cAMP/PKA/CREB axis.

► TCM Multi-Target Regulation

• Scutellaria baicalensis-Coptis chinensis Herb Pair: Modulates cytokine signaling, oxidative stress, and apoptosis pathways via AKT1, IL-6, TNF, etc., with core targets including CASP3 and PTGS2 ^[2].
• Artemisinin: Targets GALNT2, BMP7, and TGFBR2 to regulate immunity and inflammation, with structure optimization via computer-aided design ^[3].

► Novel Targets and Technologies

• Epigenetic Regulation: A Zhejiang University team discovered that enhancer RNA at the Sirpa locus regulates macrophage SIRPα expression, emerging as a UC target. Antisense oligonucleotides validated efficacy in murine models.
• Protein Interaction Targets: PDIA1 overexpression in UC intestinal epithelia impairs barrier function; its inhibition is under drug screening. Macrophage-specific NOC4L knockout alleviates UC symptoms, showing diagnostic and therapeutic potential.
• Nanomedicine: Nanoparticle-based drug delivery systems modulate macrophage polarization, reducing pro-inflammatory cytokines (IL-1β, TNF-α).

CUSABIO specializes in providing high-quality research tools, including proteins, antibodies, and ELISA kits. Below is a curated list of popular UC-related targets and reagents for your research needs:

Ulcerative Colitis Drug Targets Related Products

● Target Proteins

CD40
CSB-MP004936HU1

Measured by its binding ability in a functional ELISA. Immobilized CD40 at 2 μg/ml can bind CD40L (CSB-MP004937HU3), the EC₅₀ is 3.112-3.858 ng/ml.

CTLA4
CSB-MP006163HU1

Measured by its binding ability in a functional ELISA. Immobilized CD152 at 2 μg/ml can bind Anti-CD152 rabbit monoclonal antibody(CSB-RA213310A0HU), the EC₅₀ of human CD152 protein is 27.14-34.82 ng/ml.

IL2RA
CSB-MP011649HU3

Measured by its binding ability in a functional ELISA. Immobilized Human IL2RA at 2μg/mL can bind Anti-IL2RA recombinant antibody (CSB-RA011649MA1HU)，the EC₅₀ is 2.463-3.353 ng/mL.

IL4R
CSB-MP011661HU2-B

Measured by its binding ability in a functional ELISA. Immobilized Human IL4(CSB-MP011659HU) at 2μg/mL can bind biotinylated Human IL4R，the EC₅₀ is 12.68-14.23 ng/mL

MS4A1
CSB-MP015007HU

Measured by its binding ability in a functional ELISA. Immobilized human CD20 at 2 μg/ml can bind Anti-CD20 recombinant antibody (CSB-RA015007A1HU), the EC₅₀ is 3.243-7.085 ng/mL.

PDCD1
CSB-MP619964HU1

Measured by its binding ability in a functional ELISA. Immobilized PD-1 at 2 μg/ml can bind Anti-PD-1 recombinant antibody, the EC₅₀ of human PD-1 protein is 6.087-7.854 ng/ml.

TNFSF15
CSB-MP023992HU(F2)

Measured by its binding ability in a functional ELISA. Immobilized Human TNFSF15 at 2 μg/ml can bind Anti-TNFSF15 recombinant antibody(CSB-RA023992MA1HU). The EC₅₀ is 0.8389-0.9731 ng/mL

TNFSF8
CSB-MP023996HU1

Measured by its binding ability in a functional ELISA. Immobilized CD30(CSB-MP023983HU1h6) at 5 μg/ml can bind human CD30L, the EC₅₀ is 9.531-12.49 ng/ml.