NPASS Compound

Natural Product: NPC606650

Natural Product ID	NPC606650
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	TUTLRKKYUXPDGN-OAHLLOKOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2334880
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 43 47 0 0 0 0 0 0 0 0999 V2000 -4.9874 -0.7156 1.5860 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3431 -0.6141 0.3502 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5655 0.4395 -0.0557 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1236 1.5183 -0.7232 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4852 1.5133 -0.9739 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2936 2.5502 -1.1080 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9444 2.4904 -0.8258 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3601 1.4241 -0.1599 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1996 0.4013 0.2184 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6683 -0.7897 0.9396 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2854 -0.9719 0.6283 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0638 -1.4543 -0.7185 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2394 -2.2559 -0.6672 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2790 -1.3129 -0.1610 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5898 -1.6307 -0.4426 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6284 -0.8073 -0.0094 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3007 0.3256 0.7039 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9781 0.6293 0.9776 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9383 -0.1815 0.5522 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5310 0.1840 0.8692 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1040 1.4000 0.1250 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5223 0.9344 0.9939 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5621 0.0160 0.7611 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0084 -0.8843 -0.1486 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1210 0.3246 1.9732 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4402 -1.3005 2.3429 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9604 -1.2265 1.4197 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0129 0.6861 -1.2164 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7403 3.3944 -1.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3054 3.3129 -1.1366 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7694 -0.6686 2.0377 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2271 -1.6704 0.5591 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1680 -0.5497 -1.3433 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8969 -2.0297 -1.1180 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0869 -3.0361 0.1269 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4918 -2.6821 -1.6401 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8321 -2.5272 -1.0060 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7905 1.5417 1.5470 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5196 0.4409 1.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6102 1.5161 -0.8568 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3213 2.3285 0.7216 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8387 -0.5551 1.6841 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4530 0.4924 0.3001 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 4 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 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 17 22 1 0 22 23 1 0 23 24 1 0 9 3 1 0 20 11 1 0 21 8 1 0 19 14 1 0 24 16 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 0 6 29 1 0 7 30 1 0 10 31 1 0 10 32 1 0 12 33 1 0 12 34 1 0 13 35 1 0 13 36 1 0 15 37 1 0 18 38 1 0 20 39 1 1 21 40 1 0 21 41 1 0 23 42 1 0 23 43 1 0 M END

Standard InCHIKey	TUTLRKKYUXPDGN-OAHLLOKOSA-N
Standard InCHI	InChI=1S/C19H19NO4/c1-22-19-14-9-20-5-4-12-7-17-18(24-10-23-17)8-13(12)15(20)6-11(14)2-3-16(19)21/h2-3,7-8,15,21H,4-6,9-10H2,1H3/t15-/m1/s1
SMILES	COc1c(O)ccc2c1CN1CCc3cc4c(cc3[C@H]1C2)OCO4

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
NPO44219	Thalictrum fendleri Engelm.	Genus	Ranunculaceae	Eukaryota	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	4
Inhibition	4

Activity Type	# Activity
Individual protein	8

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	Ki	=	565.0	nM	PMID[23332346]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	Inhibition	=	25.3	%	PMID[23332346]
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	Inhibition	=	40.5	%	PMID[23332346]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	Ki	n.a.	n.a.	n.a.	PMID[23332346]
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	Inhibition	=	95.8	%	PMID[23332346]
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	Ki	n.a.	n.a.	n.a.	PMID[23332346]
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	Ki	n.a.	n.a.	n.a.	PMID[23332346]
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	Inhibition	=	63.6	%	PMID[23332346]

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 NPC606650 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	29416
0.1-0.2	18027
0.2-0.3	2095
0.3-0.4	236
0.4-0.5	43
0.5-0.6	17
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8727	High Similarity	NPC39701
0.8727	High Similarity	NPC184026
0.7333	Intermediate Similarity	NPC189266
0.7333	Intermediate Similarity	NPC172765
0.7333	Intermediate Similarity	NPC2413
0.7333	Intermediate Similarity	NPC110416
0.7213	Intermediate Similarity	NPC216459
0.7213	Intermediate Similarity	NPC41178
0.7213	Intermediate Similarity	NPC138487
0.7097	Intermediate Similarity	NPC312025
0.6825	Remote Similarity	NPC326205
0.6774	Remote Similarity	NPC31311
0.6774	Remote Similarity	NPC234392
0.6769	Remote Similarity	NPC276944
0.6769	Remote Similarity	NPC238530
0.6471	Remote Similarity	NPC232514
0.625	Remote Similarity	NPC469817
0.6129	Remote Similarity	NPC210437
0.6129	Remote Similarity	NPC16107
0.6129	Remote Similarity	NPC106295
0.6032	Remote Similarity	NPC51957
0.5821	Remote Similarity	NPC204828
0.5821	Remote Similarity	NPC295691
0.5821	Remote Similarity	NPC207757
0.5821	Remote Similarity	NPC54379
0.5821	Remote Similarity	NPC5238
0.5758	Remote Similarity	NPC276588
0.5758	Remote Similarity	NPC127674
0.5758	Remote Similarity	NPC278799
0.5667	Remote Similarity	NPC128019
0.5507	Remote Similarity	NPC264850
0.5455	Remote Similarity	NPC151895
0.5429	Remote Similarity	NPC2314
0.5231	Remote Similarity	NPC111485
0.5231	Remote Similarity	NPC88249
0.5231	Remote Similarity	NPC220858
0.5205	Remote Similarity	NPC320223
0.5077	Remote Similarity	NPC185467

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC606650 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4993
0.1-0.2	3975
0.2-0.3	166
0.3-0.4	14
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6129	Remote Similarity	NPD4584	Phase 2

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