NPASS Compound

Natural Product: NPC609472

Natural Product ID	NPC609472
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CQKMBZHLOYVGHW-QYYRPYCUSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL133809
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 33 35 0 0 0 0 0 0 0 0999 V2000 5.0383 0.8836 0.7609 N 0 0 0 0 0 0 0 0 0 0 0 0 3.9094 0.7915 -0.0986 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8131 1.3659 -1.2900 N 0 0 0 0 0 0 0 0 0 0 0 0 2.6859 1.2169 -2.0386 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6382 0.4910 -1.6067 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6876 -0.1198 -0.3885 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8338 0.0375 0.3616 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6116 -0.6571 1.4913 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3970 -1.2331 1.4823 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8409 -0.8876 0.3082 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.4890 -1.2855 -0.1486 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9675 -0.4508 -1.1212 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2391 -0.0522 -0.7971 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6097 1.2659 -1.4331 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7731 2.2836 -1.0464 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1681 0.0724 0.7223 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4273 0.1032 1.2997 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4515 -1.2543 1.0141 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4254 -2.3011 0.8110 N 0 0 0 0 0 0 0 0 0 0 0 0 5.5483 0.0451 1.1182 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3538 1.8419 1.0339 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6945 1.7206 -2.9977 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9612 -1.8564 2.2790 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4334 -2.3316 -0.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9840 -0.8272 -1.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6498 1.5175 -1.1360 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5976 1.1084 -2.5288 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1464 2.8375 -0.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5425 0.9380 0.9502 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4516 0.7864 2.0141 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9724 -1.2605 1.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2793 -2.8281 -0.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4057 -1.9614 0.9388 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 7 2 1 0 18 11 1 0 10 6 1 0 1 20 1 0 1 21 1 0 4 22 1 0 9 23 1 0 11 24 1 6 13 25 1 1 14 26 1 0 14 27 1 0 15 28 1 0 16 29 1 6 17 30 1 0 18 31 1 1 19 32 1 0 19 33 1 0 M END

Standard InCHIKey	CQKMBZHLOYVGHW-QYYRPYCUSA-N
Standard InCHI	InChI=1S/C10H14N6O3/c11-5-7(18)4(1-17)19-10(5)16-3-15-6-8(12)13-2-14-9(6)16/h2-5,7,10,17-18H,1,11H2,(H2,12,13,14)/t4-,5-,7-,10-/m1/s1
SMILES	Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1N

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO47710	Actinomadura sp. No. SA-4427	Genus	Thermomonosporaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Ki	5

Activity Type	# Activity
Individual protein	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT218	Individual protein	Adenosine A3 receptor	Homo sapiens	Ki	=	1000000.0	nM	PMID[11708915]
NPT1315	Individual protein	Adenosine A1 receptor	Rattus norvegicus	Ki	>	10.0	nM	PMID[11708915]
NPT1316	Individual protein	Adenosine A2a receptor	Rattus norvegicus	Ki	>	10.0	nM	PMID[11708915]
NPT218	Individual protein	Adenosine A3 receptor	Homo sapiens	Ki	=	301.0	nM	PMID[11708915]
NPT1760	Individual protein	Adenosine A3 receptor	Rattus norvegicus	Ki	>	10.0	nM	PMID[11708915]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC609472 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	35905
0.1-0.2	13750
0.2-0.3	96
0.3-0.4	46
0.4-0.5	33
0.5-0.6	15
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6786	Remote Similarity	NPC156461
0.6786	Remote Similarity	NPC107374
0.6786	Remote Similarity	NPC600382
0.6786	Remote Similarity	NPC612067
0.6667	Remote Similarity	NPC209525
0.6667	Remote Similarity	NPC161659
0.6441	Remote Similarity	NPC309832
0.6429	Remote Similarity	NPC317821
0.6379	Remote Similarity	NPC229974
0.6207	Remote Similarity	NPC33996
0.5938	Remote Similarity	NPC211025
0.5714	Remote Similarity	NPC136349
0.5714	Remote Similarity	NPC219313
0.5692	Remote Similarity	NPC85689
0.5672	Remote Similarity	NPC328479
0.5574	Remote Similarity	NPC604998
0.5294	Remote Similarity	NPC185991
0.5294	Remote Similarity	NPC321814
0.5217	Remote Similarity	NPC121222
0.5143	Remote Similarity	NPC164952
0.5135	Remote Similarity	NPC325906
0.5135	Remote Similarity	NPC606116
0.507	Remote Similarity	NPC302778
0.507	Remote Similarity	NPC329404
0.507	Remote Similarity	NPC212551

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC609472 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6868
0.1-0.2	2092
0.2-0.3	121
0.3-0.4	40
0.4-0.5	19
0.5-0.6	5
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6786	Remote Similarity	NPD249	Phase 4
0.6786	Remote Similarity	NPD250	Phase 4
0.5902	Remote Similarity	NPD193	Phase 2
0.5714	Remote Similarity	NPD548	Clinical (unspecified phase)
0.5294	Remote Similarity	NPD283	Phase 4
0.5143	Remote Similarity	NPD4171	Clinical (unspecified phase)
0.5135	Remote Similarity	NPD1777	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data