NPASS Compound

Natural Product: NPC276110

Natural Product ID	NPC276110
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6Alpha,8Alpha,23-Trihydroxy-Labd-13(14),17-Dien-16(R),19-Olide
IUPAC Name	(2R)-2-[(E)-5-[(1R,2R,4S,4aR,5R,8aS)-2,4-dihydroxy-5-(hydroxymethyl)-2,5,8a-trimethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL497827
PubChem CID	44157592
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 70 72 0 0 0 0 0 0 0 0999 V2000 2.9485 2.7725 1.7147 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2960 1.8255 0.7376 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0818 0.9415 0.1814 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5635 0.8772 0.5048 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8177 -0.5207 1.0827 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2394 -0.6195 1.4071 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7743 -1.5903 0.7191 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7463 -2.1970 -0.1038 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8968 -3.1667 -0.9018 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5670 -1.5177 0.1453 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9012 0.3024 2.3980 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8090 1.9623 0.4779 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3672 0.9278 -0.5111 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0184 0.8827 -0.9609 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1648 0.6315 -0.0853 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0201 0.8755 1.3631 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3390 1.5445 -0.5194 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4964 1.3566 0.3841 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9251 -0.0100 0.6732 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9175 -1.1154 0.5040 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5194 -1.7801 1.8002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7123 -2.2131 -0.2517 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1599 -1.7520 -1.4752 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7843 -0.7488 -0.3861 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6548 -1.7076 -0.4752 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9520 -1.4069 -1.8099 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0719 0.0026 -2.2249 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1571 0.3480 -3.0583 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1431 0.3246 -3.0461 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0245 -3.0365 -0.5728 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3973 2.2025 2.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1839 3.4441 2.1776 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7313 3.3728 1.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6721 0.2360 -0.5295 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8525 1.6598 1.1997 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0795 0.8969 -0.4764 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1823 -0.6589 1.9950 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8347 -1.8815 0.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6705 1.3280 2.0657 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9763 0.0848 2.4860 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3937 0.1077 3.3725 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5909 3.0025 0.1281 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3197 1.8617 1.4537 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0800 1.0973 -1.3813 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7568 -0.0420 -0.1018 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2153 1.9345 -1.4225 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9628 0.5966 1.9042 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2460 0.3436 1.8952 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9360 1.9637 1.5463 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6524 1.2480 -1.5408 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0230 2.5999 -0.5008 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3433 1.9490 -0.0907 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3092 1.9748 1.3133 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8832 -0.2063 0.1370 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2459 -0.0619 1.7593 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0937 -1.3645 2.6798 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7489 -2.8736 1.8363 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4152 -1.7377 1.9844 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6729 -2.3693 0.3479 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2304 -3.1780 -0.2348 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8198 -2.3382 -2.1784 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2442 -0.7026 -1.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9508 -1.6429 0.3801 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3032 -2.0730 -2.6109 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1215 -1.6543 -1.6342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0403 0.0344 -4.1453 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0439 -0.2527 -2.8010 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3254 1.4351 -3.1582 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9506 1.0263 -3.6898 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1875 -3.5556 -0.7119 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 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 6 11 1 0 2 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 20 22 1 0 22 23 1 0 20 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 6 25 30 1 0 10 5 1 0 27 14 1 0 24 15 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 1 7 38 1 0 11 39 1 0 11 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 6 16 47 1 0 16 48 1 0 16 49 1 0 17 50 1 0 17 51 1 0 18 52 1 0 18 53 1 0 19 54 1 0 19 55 1 0 21 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 22 60 1 0 23 61 1 0 24 62 1 6 25 63 1 1 26 64 1 0 26 65 1 0 28 66 1 0 28 67 1 0 28 68 1 0 29 69 1 0 30 70 1 0 M END

Standard InCHIKey	NMCFENXKFAREEU-FTZSKZMTSA-N
Standard InCHI	InChI=1S/C25H40O5/c1-16(7-9-19-17(2)13-21(28)30-19)8-10-20-24(4)12-6-11-23(3,15-26)22(24)18(27)14-25(20,5)29/h7,13,18-20,22,26-27,29H,6,8-12,14-15H2,1-5H3/b16-7+/t18-,19+,20+,22-,23-,24+,25+/m0/s1
SMILES	C/C(=CC[C@@H]1C(=CC(=O)O1)C)/CC[C@@H]1[C@@]2(C)CCC[C@@](C)(CO)[C@@H]2[C@H](C[C@@]1(C)O)O

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
NPO33075	salvia dominica	Species	Lamiaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[19459643]
NPO40338	Salvia tingitana	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32182064]

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
Kd	1
MIC	22

Activity Type	# Activity
Individual protein	1
Organism	22

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6478	Individual protein	Tubulin--tyrosine ligase	Homo sapiens	Kd	=	72.0	nM	PMID[211235]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4427	Organism	Staphylococcus simulans	Staphylococcus simulans	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT3599	Organism	Staphylococcus capitis	Staphylococcus capitis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT5312	Organism	Staphylococcus warneri	Staphylococcus warneri	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4840	Organism	Staphylococcus lugdunensis	Staphylococcus lugdunensis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4075	Organism	Enterococcus avium	Enterococcus avium	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4844	Organism	Enterococcus gallinarum	Enterococcus gallinarum	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT1863	Organism	Staphylococcus saprophyticus	Staphylococcus saprophyticus	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4025	Organism	Staphylococcus hominis	Staphylococcus hominis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT3730	Organism	Enterococcus durans	Enterococcus durans	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT1477	Organism	Staphylococcus haemolyticus	Staphylococcus haemolyticus	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT23872	Organism	Enterococcus casseliflavus	Enterococcus casseliflavus	MIC	>	128.0	ug.mL-1	PMID[32182064]

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 NPC276110 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	15933
0.1-0.2	25115
0.2-0.3	8550
0.3-0.4	231
0.4-0.5	13
0.5-0.6	5
0.6-0.7	7
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8276	Intermediate Similarity	NPC120321
0.8	Intermediate Similarity	NPC489648
0.7627	Intermediate Similarity	NPC38855
0.7458	Intermediate Similarity	NPC489647
0.6471	Remote Similarity	NPC476081
0.6308	Remote Similarity	NPC489641
0.6308	Remote Similarity	NPC306265
0.625	Remote Similarity	NPC278673
0.6212	Remote Similarity	NPC222927
0.6119	Remote Similarity	NPC187435
0.6029	Remote Similarity	NPC489646
0.5857	Remote Similarity	NPC489644
0.5775	Remote Similarity	NPC120009
0.5614	Remote Similarity	NPC63958
0.5294	Remote Similarity	NPC53555
0.5143	Remote Similarity	NPC179380

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC276110 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6213
0.1-0.2	2748
0.2-0.3	186
0.3-0.4	3
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