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 11: RNA-Binding & PTM Context Analysis
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 |
| Small molecule | CHEMBL496594 | N#Cc1cnc2c(Cl)cc(NCc3cn(CCN4CCCCCC4)nn3)… | 553.47 | 6.38 | 94.69 | 4 | 5 | 1 | 1 | 3 | 4 | 5 | N#Cc1cnc2c(Cl)cc(NCc3cn(CCN4CCCCCC4)nn3)… | CHEMBL496594 | 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 | CHEMBL160571 | CCCNC(=O)N(O)c1cc([C@H]2CC[C@H](c3cc(OC)… | 546.66 | 6.20 | 107.95 | 4 | 5 | 1 | 1 | 2 | 5 | 4 | CCCNC(=O)N(O)c1cc([C@H]2CC[C@H](c3cc(OC)… | CHEMBL160571 | tool | tool | |||
| Small molecule | CHEMBL160839 | CCCOc1cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC… | 532.63 | 5.81 | 107.95 | 4 | 5 | 1 | 1 | 2 | 5 | 4 | CCCOc1cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC… | CHEMBL160839 | tool | tool | |||
| Small molecule | CHEMBL3972603 | O=C(O)c1ccc(S(=O)(=O)N(Cc2ccc(OC(F)(F)F)… | 547.58 | 6.77 | 83.91 | 4 | 5 | 1 | 1 | 3 | 1 | 5 | O=C(O)c1ccc(S(=O)(=O)N(Cc2ccc(OC(F)(F)F)… | CHEMBL3972603 | 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 | CHEMBL3913523 | CCN(CC)CCOc1cc2c(cc1N1CCC(N3CCOCC3)CC1)C… | 569.75 | 4.93 | 84.83 | 4 | 5 | 1 | 1 | 3 | 2 | 4 | CCN(CC)CCOc1cc2c(cc1N1CCC(N3CCOCC3)CC1)C… | CHEMBL3913523 | 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 | 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 | 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 | CHEMBL6068504 | COc1ccc(OC)c2[nH]c(CCCN(C)CC[C@]3(OC(=O)… | 545.72 | 6.29 | 76.68 | 4 | 5 | 1 | 1 | 3 | 1 | 3 | COc1ccc(OC)c2[nH]c(CCCN(C)CC[C@]3(OC(=O)… | ACT-280778 | tool | tool | |||
| Small molecule | CHEMBL3655685 | N=C(N)c1cccc(CC(NS(=O)(=O)c2cccc(-c3ccc(… | 549.70 | 2.09 | 181.28 | 4 | 5 | 1 | 1 | 1 | 2 | 4 | N=C(N)c1cccc(CC(NS(=O)(=O)c2cccc(-c3ccc(… | CHEMBL3655685 | tool | tool | |||
| Small molecule | CHEMBL4303303 | Cc1cc(Nc2ncnc3ccc(-c4ccc(CNCCS(C)(=O)=O)… | 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: 0.8581, Budget Used: 1.72%, Budget Remaining: $49.1419
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=0.0354 time=284s, EXECUTOR GREEN cost=$0.0195 time=9975s, MCDA Validity Summary: overall_verdict: valid_ranking, entities scored: 45, 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 | 1.72 |
| Budget Remaining Usd | 49.1419 |
| Tasks Completed | 4 |
| Risks Identified | 3 |
Agent Alert Levels
Agent Alert Levels (server-queried — not from compressed text):
PLANNER GREEN cost=$0.0024 time=19s
LEARNER GREEN cost=$0.0354 time=284s
EXECUTOR GREEN cost=$0.0195 time=9975s
A.G.E. Scores
(No AGE scores this cycle)
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