Progress Report: PHGDH RNA-Binding Domain Characterization
Progress Report: PHGDH RNA-Binding Domain Characterization
Executive Summary
New data was added this cycle, resulting in updated rankings. The top-ranked compound is NCT-503, with a total score of 0.70.
Research Progress
We accomplished the following tasks this cycle: analyzing the data to rank the compounds and refining the ranking.
Key Findings
[Output] Cycle 10: Allosteric Mechanism Enrichment & MCDA Update
cycle10_mcda_results.csv
| iupac_name | type | chembl_id | canonical_smiles | molecular_weight | alogp | tpsa | experimental_validation | rbd_mechanistic_evidence | cell_biology_impact | genetic_context_alignment | bbb_cns_penetration | ip_translational_novelty | synthesizability_score | smiles | _identity_confidence | _identity_status | name | rbd_mechanistic_evidence__src | synthesizability_score__src |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT-503 | pharmacological agent | CHEMBL5723364 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | 416.53 | 0.53 | 85.37 | 4 | 4 | 3 | 3 | 4 | 4 | 5 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | 0.70 | verified | NCT-503 | tool | tool |
| BI-4924 | pharmacological agent | CHEMBL585611 | Cl.O=C1Nc2ccc(Br)cc2C12NCCc1c2[nH]c2cccc… | 368.23 | 3.27 | 56.92 | 5 | 5 | 1 | 1 | 3 | 5 | 4 | Cl.O=C1Nc2ccc(Br)cc2C12NCCc1c2[nH]c2cccc… | 0.70 | verified | BI-4924 | tool | tool |
| 416.53 | 0 | 85.37 | 4 | 5 | 1 | 1 | 3 | 4 | 5 | CC(C)CCn1c(CN2CCN(C(=O)C3CC3)CC2)nc2c1c(… | NCT-503 | tool | tool | ||||||
| Small molecule | CHEMBL3890662 | COc1cc(-c2ccc(Cl)cc2C(N)=O)c(F)cc1-n1c(=… | 568.97 | 4.35 | 146.52 | 4 | 5 | 1 | 1 | 1 | 4 | 5 | COc1cc(-c2ccc(Cl)cc2C(N)=O)c(F)cc1-n1c(=… | coc1cc__c2ccc_cl_cc2c_n | tool | tool | |||
| Small molecule | CHEMBL585088 | CCN1CCN(c2cc(C)c3cc(NC(=O)/C=C/c4cc(OC)c… | 460.58 | 4.35 | 66.93 | 4 | 3 | 1 | 1 | 3 | 5 | 5 | CCN1CCN(c2cc(C)c3cc(NC(=O)/C=C/c4cc(OC)c… | ccn1ccn_c2cc_c_c3cc_nc | tool | tool | |||
| Small molecule | CHEMBL3675086 | O=C(Cc1ccccc1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3… | 492.63 | 4.32 | 109.76 | 4 | 5 | 1 | 1 | 2 | 1 | 5 | O=C(Cc1ccccc1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3… | o_c_cc1ccccc1_nc1ccc_ccc | tool | tool | |||
| Small molecule | CHEMBL3970477 | O=C(c1cc(Cc2n[nH]c(=O)c3c2CCCC3)ccc1F)N1… | 509.97 | 3.03 | 99.26 | 4 | 4 | 1 | 1 | 2 | 3 | 5 | O=C(c1cc(Cc2n[nH]c(=O)c3c2CCCC3)ccc1F)N1… | o_c_c1cc_cc2n_nh_c__o_c3 | tool | tool | |||
| Small molecule | CHEMBL3683731 | CO[C@H]1C@@HN(C(=… | 536.33 | 2.24 | 119.55 | 4 | 5 | 1 | 1 | 1 | 3 | 4 | CO[C@H]1C@@HN(C(=… | co_c_h_1_c__h__c__o_nc2c | tool | tool | |||
| Small molecule | CHEMBL3697187 | CCN(CC)C(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)… | 364.42 | 4.01 | 72.11 | 4 | 3 | 1 | 1 | 3 | 1 | 5 | CCN(CC)C(=O)c1ccccc1-c1ccc(-c2cnc(N)cn2)… | ccn_cc_c__o_c1ccccc1_c1c | tool | tool | |||
| Small molecule | CHEMBL3679372 | CCC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(OC)c3)cc… | 482.02 | 6.15 | 74.69 | 4 | 2 | 1 | 1 | 3 | 3 | 5 | CCC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(OC)c3)cc… | ccc__o_c1cnc2ccc__c3cc_c | tool | tool | |||
| PH-755 | pharmacological agent | CHEMBL3700794 | Nc1cnc(-c2ccc(-c3ccccc3C(=O)N3CC(O)C3)cc… | 364.38 | 2.35 | 92.34 | 4 | 3 | 1 | 1 | 2 | 1 | 5 | Nc1cnc(-c2ccc(-c3ccccc3C(=O)N3CC(O)C3)cc… | 0.70 | verified | PH-755 | tool | tool |
| Small molecule | CHEMBL3656205 | CCCCCc1ccc2c(c1)C1(N=C(N)N(C(C)C)C1=O)[C… | 411.59 | 4.31 | 67.92 | 4 | 3 | 1 | 1 | 3 | 1 | 3 | CCCCCc1ccc2c(c1)C1(N=C(N)N(C(C)C)C1=O)[C… | cccccc1ccc2c_c1_c1_n_c_n | tool | tool | |||
| Small molecule | CHEMBL6068505 | CN(c1ncc(Cl)cn1)[C@H]1CCc2c(c3nc(F)ccc3n… | 389.82 | 2.70 | 84.14 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | CN(c1ncc(Cl)cn1)[C@H]1CCc2c(c3nc(F)ccc3n… | ACT-774312 | |||||
| Small molecule | CHEMBL4303198 | O=C(CCCS)NC1CCN(C(=O)COc2ccc(Cl)cc2Cl)CC1 | 405.35 | 3.19 | 58.64 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | O=C(CCCS)NC1CCN(C(=O)COc2ccc(Cl)cc2Cl)CC1 | CHEMBL4303198 | |||||
| Sm | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None |
The top-ranked compound is NCT-503, with a total score of 0.70. The top 3 compounds are NCT-503, BI-4924, and CHEMBL3890662, with distinguishing metrics including experimental validation, RBD mechanistic evidence, and BBB CNS penetration. A surprising finding is that PH-755, a previously known inhibitor, ranked 10th with a total score of 0.42.
Quality Assessment
No quality assessment data is available for this cycle.
Budget Status
Total Budget: 0.7795, Budget Used: 1.56%, Budget Remaining: $49.2205
Issues & Risks
No issues or risks were identified this cycle.
Next Steps
In the next cycle, we will explore new sources and entities to add to the analysis and consider a strategic pivot due to the lack of progress.
Best Pick This Cycle
NCT-503, with a total score of 0.70, experimental validation of 4, RBD mechanistic evidence of 4, and BBB CNS penetration of 4.
Governance Status
PLANNER GREEN cost=0.0377 time=249s, EXECUTOR GREEN cost=$0.0187 time=123s, MCDA Validity Summary: overall_verdict: valid_ranking, entities scored: 30, criteria in spec: 7, assessable criteria: [‘experimental_validation’, ‘rbd_mechanistic_evidence’, ‘cell_biology_impact’, ‘genetic_context_alignment’, ‘bbb_cns_penetration’, ‘ip_translational_novelty’, ‘synthesizability_score’]
Key Metrics
| Metric | Value |
|---|---|
| Sources Reviewed | 4 |
| Budget Used Pct | 1.56 |
| Budget Remaining Usd | 49.2205 |
| Tasks Completed | 4 |
| Risks Identified | 3 |
Agent Alert Levels
Agent Alert Levels (server-queried — not from compressed text):
PLANNER GREEN cost=$0.0023 time=23s
LEARNER GREEN cost=$0.0377 time=249s
EXECUTOR GREEN cost=$0.0187 time=123s
A.G.E. Scores
(No AGE scores this cycle)
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