Market Intelligence, Clinical Progress, and High-Purity Reagents for DDR-Targeted Therapy Development
Target Identity & Functional Domains
ATR (Ataxia Telangiectasia and Rad3-related), also known as FRP1, is a core PIKK family kinase in the DNA damage response (DDR). The primary UniProt entry (Q13535) confirms three key functional domains: a FAT domain, a PI3K/PI4K catalytic domain, and a FATC domain. Clinically relevant mutations include rs35306038, rs28897763, and rs2227928 (dbSNP). The resolved target is ATR, with FRP1 as an alias.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for ATR/FRP1 drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Active Kinase (WT & Mutant) | ATR Kinase Domain (Human) – high purity (>90%), Endotoxin <1 EU/μg, sequence verified, theoretical MW confirmed by mass spec. Suitable for biochemical assays and selectivity panels. | View ATR Products |
| Gene Delivery | ATR-ORF Lentivirus Premade Particles – full-length ORF for stable cell line construction. HEK293T packaged, titer >1×10⁸ TU/mL. | View ATR Products |
| Benchmark Antibody | Anti-ATR/FRP1 Recombinant Antibody (phospho-specific/total) – positive control for target engagement and Western blot. | View ATR Products |
| Validator (siRNA) | ATR siRNA Set (3 target-specific + 1 control) – for synthetic lethality validation and specificity controls. | View ATR Products |
| Related Target: ATRIP | Essential interacting partner required for ATR recruitment to RPA-coated ssDNA. | View ATRIP Products |
| Related Target: ATM | Parallel DDR pathway kinase; essential for synthetic lethality screening and selectivity assays. | View ATM Products |
| Related Target: CHK1 (CHEK1) | Primary substrate of ATR; critical for cellular DDR biomarker assays (e.g., pCHK1 Ser345). | View CHEK1 Products |
| Related Target: PARP1 | Synthetic lethal combination partner; combination therapy target for DDR-deficient tumors. | View PARP1 Products |
Critical Assay Challenges & The TarMart Advantage
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| PIKK Family Selectivity & Off-target Screening (vs. ATM, DNA-PKcs, mTOR) | Highly purified recombinant ATR Kinase Domain (>90% purity, endotoxin <1 EU/μg) with native ATP-binding conformation; parallel ATM and DNA-PKcs proteins available for selectivity index determination. |
| Cellular DDR Context Loss (Biochemical vs. Cellular disconnect) | Lentivirus-based stable cell lines (HEK293T backbone) expressing full-length ATR-WT or mutants; preserves physiological complexes with ATRIP for accurate cellular readouts (pCHK1, pRPA32, γH2AX). |
| Drug Resistance Modeling & Mutant Profiling | Custom mutant ATR kinase proteins (sequence‑verified) covering clinical resistance hotspots; expedite mechanism‑of‑resistance studies and next‑generation inhibitor screening. |
| Target Validation & Synthetic Lethality | Validated ATR siRNA sets plus benchmark antibodies (phospho-specific/total) for definitive knockdown confirmation and pathway specificity checks; essential for ATM‑deficient background studies. |
Live ATR R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for ATR/FRP1 therapeutics is intensifying, with major players shifting focus from monotherapy to biomarker‑driven combination regimens and synthetic lethality strategies. First‑generation inhibitors (Ceralasertib/AZD6738 from AstraZeneca, Camonsertib/RP‑3500 from Repare Therapeutics, Elimusertib/BAY 1895344 from Bayer) are advancing through Phase II/III trials in ATM‑deficient solid tumors, ovarian cancer, and gastric cancer. The next wave of R&D is targeting rational combinations with PARP inhibitors (to overcome PARPi resistance), immune checkpoint blockade, and platinum‑based chemotherapy. Emerging modalities include CNS‑penetrant analogs for brain metastases and PROTAC degraders aimed at refractory tumors. The therapeutic window remains a challenge, driving the need for highly selective inhibitors and robust biomarker assays.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Small Molecule Inhibitor (Selective) | AstraZeneca, Repare Therapeutics, Bayer, Merck KGaA | ATM‑deficient solid tumors, ovarian, gastric, NSCLC | Kinase selectivity panel (need purified ATR, ATM, DNA‑PKcs proteins for off‑target screening) |
| Small Molecule (CNS‑Penetrant) | Merck (Artios Pharma), various biotechs | Brain metastases, glioblastoma | Cellular DDR assays with lentivirus‑stable cell lines for BBB penetration correlation |
| PROTACs / Degraders | Emerging biotechs | Refractory/relapsed solid tumors | Degradation validation (need HEK293‑expressed targets & lentivirus for stable overexpression) |
| Combination (PARPi + ATRi) | AstraZeneca, Artios Pharma | BRCA1/2‑mutant, platinum‑resistant ovarian | Synthetic lethality validation (need ATR siRNA + PARP1 protein tools) |
| Radiosensitizer / Chemo Combo | Bayer, Merck KGaA, academic consortia | Locally advanced solid tumors | Phosphorylation biomarker assays (need recombinant CHK1/RPA32 substrates) |
Key Mutations & Resistance Profiling
Clinically relevant ATR mutations from dbSNP (UniProt VAR_041584, VAR_041585, VAR_050532) include rs35306038, rs28897763, and rs2227928. These variants may impact ATP‑binding affinity or compound sensitivity. TarMart offers custom mutant ATR kinase proteins (sequence‑verified) to support resistance mechanism studies and next‑generation inhibitor development.