NPASS Compound

Natural Product: NPC109376

Natural Product ID	NPC109376
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Argutin A
IUPAC Name	[(1S,3R,5R,6aS,7R,8R,10R,10aS)-1,3-diacetyloxy-10-hydroxy-7,8-dimethyl-7-[(2E)-3-methylpenta-2,4-dienyl]-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] (2Z,4E)-deca-2,4-dienoate
Synonyms	Argutin A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1651112
PubChem CID	53322249
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

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 90 92 0 0 0 0 0 0 0 0999 V2000 9.0030 -1.5892 -2.6211 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5827 -1.1127 -2.7272 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1400 -0.3868 -1.4632 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7067 0.0549 -1.6597 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2041 0.7791 -0.4525 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2586 -0.0979 0.7344 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1592 -0.4190 1.4421 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3321 -1.2738 2.5697 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3432 -1.6532 3.3325 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9822 -1.2472 3.1117 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0932 -1.6936 3.9440 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4612 -0.4480 2.1442 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0596 -0.1298 2.0565 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1228 1.3504 2.2464 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1773 1.8926 1.7129 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6069 3.3170 1.7397 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5884 4.1454 1.1548 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0423 5.1912 1.8420 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4492 5.4213 3.0075 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0062 6.0388 1.2330 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6894 3.4067 0.8831 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5335 2.3437 -0.0453 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2325 1.1764 0.9140 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7214 -0.0388 0.2414 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3308 -0.4321 0.6539 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6988 -1.2291 0.2326 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8699 -2.4774 -0.1509 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6395 -1.0318 -0.8794 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6851 -1.9730 -1.1666 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7901 -2.6656 -2.3054 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7586 -2.4746 -3.3886 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9127 -3.5791 -2.4542 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0965 -4.2925 -3.5294 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1708 -1.4773 1.6021 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2533 -2.4817 1.8028 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4677 -0.2826 2.4527 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4416 1.0310 1.7627 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3853 2.0118 2.7868 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4665 2.6136 -0.9021 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6681 2.7817 -2.2770 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8752 2.6704 -2.6702 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5720 3.0691 -3.2246 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1800 -2.3470 -3.3957 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6617 -0.6859 -2.7551 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1614 -2.0491 -1.6354 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4324 -0.4262 -3.5845 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9147 -1.9787 -2.8599 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2524 -1.1004 -0.6344 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8298 0.4627 -1.3010 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1032 -0.8498 -1.8401 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7148 0.7471 -2.5384 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1774 1.1513 -0.6328 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9092 1.6374 -0.2669 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2336 -0.4791 1.0187 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2622 0.0072 1.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3522 -1.6475 2.8308 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5515 -2.3260 4.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4898 -0.6089 2.8558 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6298 1.8879 2.8157 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7959 3.7034 2.7474 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8868 6.0587 0.1275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9527 7.0725 1.6086 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0052 5.6489 1.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4972 2.2781 -0.5357 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6291 0.2294 -0.8526 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4281 0.1225 0.0154 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0886 -1.4908 0.4682 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6555 -3.2036 -0.5256 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2249 -2.2968 -1.0044 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4445 -2.9711 0.7202 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1065 0.0015 -0.7416 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0393 -0.8261 -1.8192 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4633 -2.1566 -0.4503 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7633 -3.3630 -4.0199 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9381 -1.5566 -3.9678 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7566 -2.4808 -2.8783 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6364 -3.6824 -1.6459 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4451 -4.2611 -4.3725 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9631 -4.9655 -3.5938 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2820 -1.9703 2.1337 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2779 -2.0320 1.8931 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2063 -3.3653 1.1444 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1456 -2.9501 2.8380 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7966 -0.1927 3.3593 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4912 -0.3705 2.9303 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3981 1.2634 1.2450 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2500 2.0847 3.2452 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3501 2.5358 -2.9504 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3608 4.1668 -3.2890 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9295 2.7663 -4.2310 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 16 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 26 27 1 6 26 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 26 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 37 38 1 0 22 39 1 0 39 40 1 0 40 41 2 0 40 42 1 0 25 13 1 0 23 15 1 1 37 23 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 0 2 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 5 52 1 0 5 53 1 0 6 54 1 0 7 55 1 0 8 56 1 0 9 57 1 0 13 58 1 1 14 59 1 0 16 60 1 1 20 61 1 0 20 62 1 0 20 63 1 0 22 64 1 6 24 65 1 6 25 66 1 0 25 67 1 0 27 68 1 0 27 69 1 0 27 70 1 0 28 71 1 0 28 72 1 0 29 73 1 0 31 74 1 0 31 75 1 0 31 76 1 0 32 77 1 0 33 78 1 0 33 79 1 0 34 80 1 1 35 81 1 0 35 82 1 0 35 83 1 0 36 84 1 0 36 85 1 0 37 86 1 6 38 87 1 0 42 88 1 0 42 89 1 0 42 90 1 0 M END

Standard InCHIKey	STQXAQGQWCMXAF-XMESWUDMSA-N
Standard InCHI	InChI=1S/C34H48O8/c1-8-10-11-12-13-14-15-16-30(38)41-26-20-27-31(39-24(5)35)42-32(40-25(6)36)34(27)28(21-26)33(7,18-17-22(3)9-2)23(4)19-29(34)37/h9,13-17,20,23,26,28-29,31-32,37H,2,8,10-12,18-19,21H2,1,3-7H3/b14-13+,16-15-,22-17+/t23-,26+,28+,29-,31+,32-,33-,34-/m1/s1
SMILES	CCCCC/C=C/C=CC(=O)O[C@H]1C=C2[C@@H](OC(=O)C)O[C@H]([C@]32[C@@H](C1)[C@](C)(C/C=C(C)/C=C)[C@H](C)C[C@H]3O)OC(=O)C

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
NPO22840	Casearia arguta	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21067210]
NPO22840	Casearia arguta	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21067210]
NPO22840	Casearia arguta	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
EC50	2
Ratio EC50	1

Activity Type	# Activity
Cell line	3

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT369	Cell line	ACHN	Homo sapiens	EC50	=	2400.0	nM	PMID[21376582]
NPT369	Cell line	ACHN	Homo sapiens	EC50	=	5400.0	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	Ratio EC50	=	2.3	n.a.	PMID[229223]

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 NPC109376 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	19634
0.1-0.2	26813
0.2-0.3	3250
0.3-0.4	80
0.4-0.5	21
0.5-0.6	23
0.6-0.7	13
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8077	Intermediate Similarity	NPC224660
0.7922	Intermediate Similarity	NPC316708
0.7671	Intermediate Similarity	NPC488964
0.7671	Intermediate Similarity	NPC184512
0.7571	Intermediate Similarity	NPC602188
0.75	Intermediate Similarity	NPC201880
0.726	Intermediate Similarity	NPC81567
0.726	Intermediate Similarity	NPC329623
0.726	Intermediate Similarity	NPC488652
0.726	Intermediate Similarity	NPC609711
0.72	Intermediate Similarity	NPC252296
0.7162	Intermediate Similarity	NPC330003
0.7162	Intermediate Similarity	NPC470321
0.7162	Intermediate Similarity	NPC264867
0.7162	Intermediate Similarity	NPC473207
0.7162	Intermediate Similarity	NPC609715
0.7125	Intermediate Similarity	NPC172867
0.7083	Intermediate Similarity	NPC488659
0.7083	Intermediate Similarity	NPC604149
0.7027	Intermediate Similarity	NPC134270
0.68	Remote Similarity	NPC488660
0.68	Remote Similarity	NPC488657
0.68	Remote Similarity	NPC488654
0.68	Remote Similarity	NPC609880
0.6711	Remote Similarity	NPC488658
0.6711	Remote Similarity	NPC488655
0.6707	Remote Similarity	NPC470024
0.6588	Remote Similarity	NPC470026
0.6316	Remote Similarity	NPC488653
0.6316	Remote Similarity	NPC488656
0.6154	Remote Similarity	NPC479491
0.6047	Remote Similarity	NPC470025
0.6	Remote Similarity	NPC116292
0.5949	Remote Similarity	NPC7644
0.5897	Remote Similarity	NPC479943
0.575	Remote Similarity	NPC479940
0.575	Remote Similarity	NPC316974
0.575	Remote Similarity	NPC479497
0.5679	Remote Similarity	NPC475889
0.5679	Remote Similarity	NPC7613
0.5679	Remote Similarity	NPC479942
0.5663	Remote Similarity	NPC119550
0.561	Remote Similarity	NPC479941
0.5568	Remote Similarity	NPC317460
0.5556	Remote Similarity	NPC311223
0.5506	Remote Similarity	NPC488217
0.5506	Remote Similarity	NPC488218
0.5412	Remote Similarity	NPC127933
0.5333	Remote Similarity	NPC486751
0.5301	Remote Similarity	NPC238397
0.5222	Remote Similarity	NPC321272
0.5208	Remote Similarity	NPC320734
0.5181	Remote Similarity	NPC311166
0.5176	Remote Similarity	NPC471363
0.5063	Remote Similarity	NPC603601
0.5062	Remote Similarity	NPC600724

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC109376 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7235
0.1-0.2	1883
0.2-0.3	32
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
		NPD

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