NPASS Compound

Natural Product: NPC476949

Natural Product ID	NPC476949
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(E)-4-[(1S,4aR,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-2-methylbut-2-enal
IUPAC Name	(E)-4-[(1S,4aR,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-2-methylbut-2-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	90676780
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] 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 52 53 0 0 0 0 0 0 0 0999 V2000 4.7029 0.6995 1.3250 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1308 -0.5878 0.8140 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0295 -0.5636 0.0841 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3106 0.6498 -0.2710 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9120 0.7878 0.1716 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4197 2.1181 -0.3311 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6450 3.2068 0.3570 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3115 2.0626 -1.6269 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5237 1.1595 -1.5522 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4156 0.3257 -0.3243 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0514 -0.2995 -0.2582 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0507 -1.3588 0.8585 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0915 -1.0694 1.8917 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4944 -1.0709 1.3464 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5577 -0.6021 -0.0876 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6720 -1.7345 -1.0605 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8288 0.2263 -0.3161 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9639 -0.5566 -0.1092 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2640 -0.2714 2.1915 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3454 -1.0031 -1.5138 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8197 -1.8302 1.1462 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8532 -1.8790 1.8286 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9805 1.2270 1.9853 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0044 1.3660 0.4695 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6037 0.5195 1.9101 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6551 -1.5147 -0.2635 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8649 1.5008 0.2399 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4009 0.9494 -1.3555 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8077 0.8751 1.2948 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1787 3.1608 1.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2677 4.1463 -0.0499 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4262 1.7252 -2.3942 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6024 3.1012 -1.9466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4187 1.8425 -1.5292 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5697 0.6069 -2.5045 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4586 1.0549 0.5441 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0504 -2.3843 0.4652 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9392 -1.2636 1.3847 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8325 -0.1032 2.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9959 -1.8429 2.6793 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9181 -2.0941 1.4013 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9105 -2.5010 -1.0164 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8385 -1.2934 -2.0658 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6504 -2.2497 -0.8188 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8614 0.4591 -1.4222 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8228 1.1830 0.2008 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8365 -1.1369 0.6814 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9994 0.6792 2.1578 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4606 -1.0636 -2.2765 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1920 -0.5126 -2.0346 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5876 -2.0902 -1.3139 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3738 -2.7562 0.7558 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 6 8 1 0 8 9 1 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 15 16 1 6 15 17 1 0 17 18 1 0 14 19 1 0 11 20 1 6 2 21 1 0 21 22 2 0 11 5 1 0 15 10 1 0 1 23 1 0 1 24 1 0 1 25 1 0 3 26 1 0 4 27 1 0 4 28 1 0 5 29 1 1 7 30 1 0 7 31 1 0 8 32 1 0 8 33 1 0 9 34 1 0 9 35 1 0 10 36 1 1 12 37 1 0 12 38 1 0 13 39 1 0 13 40 1 0 14 41 1 6 16 42 1 0 16 43 1 0 16 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 19 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 21 52 1 0 M END

Standard InCHIKey	XMGQNBFCAUFSGC-RXHMHPOJSA-N
Standard InCHI	InChI=1S/C19H30O3/c1-13(11-20)5-7-15-14(2)6-8-16-18(15,3)10-9-17(22)19(16,4)12-21/h5,11,15-17,21-22H,2,6-10,12H2,1,3-4H3/b13-5+/t15-,16+,17+,18+,19-/m0/s1
SMILES	C/C(=C\C[C@H]1C(=C)CC[C@@H]2[C@@]1(CC[C@H]([C@@]2(C)CO)O)C)/C=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	306.22	Volume:	338.529 ? Van der Waals volume.
Dense:	0.905	LogP:	2.917 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.119 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.023 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	14.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.476	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.475	Fsp³:	0.737
MCE-18:	43.273 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.315	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.846	Promiscuous compounds:	0.136

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.005	MDCK Permeability:	-4.838
Pgp-inhibitor:	0.031	Pgp-substrate:	0.031
PAMPA:	0.847 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.016
20% Bioavailability (F20%):	0.532	30% Bioavailability (F30%):	0.183
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.256	MRP1:	0.293
Plasma Protein Binding (PPB):	65.952%	Volume Distribution (VD):	-0.249
Fu:	33.756% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.599
BSEP inhibitor:	0.846

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	0.005
CYP2C19-inhibitor:	0.423	CYP2C19-substrate:	0.031
CYP2C9-inhibitor:	0.743	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.057	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.446	CYP3A4-substrate:	0.243
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.987
HLM stability:	0.548 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

10.099

Half-life (T1/2):

1.257

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.381
Human Hepatotoxicity (H-HT):	0.634	Drug-induced Liver Injury (DILI):	0.184
AMES Toxicity:	0.455	Rat Oral Acute Toxicity:	0.438
Maximum Recommended Daily Dose:	0.484	Skin Sensitization:	0.971
Carcinogencity:	0.863	Eye Corrosion:	0.118
Eye Irritation:	0.925	Respiratory Toxicity:	0.666
Drug-induced Neurotoxicity:	0.472	Ototoxicity:	0.333
Hematotoxicity:	0.269	Drug-induced Nephrotoxicity:	0.406
Genotoxicity:	0.712	RPMI-8226 Immunitoxicity:	0.083
A549 Cytotoxicity:	0.348	Hek293 Cytotoxicity:	0.432
BCF:	1.259 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.906 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.475 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.824 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33579	Croton laui	Species	Euphorbiaceae	Eukaryota	Twigs	Hainan Province, China	n.a.	PMID[24735527]

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
IC50	2
MIC	11

Activity Type	# Activity
Cell line	2
Organism	10
Others	1

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
NPT116	Cell line	HL-60	Homo sapiens	IC50	>=	10000	nM	PMID[24735527]
NPT168	Cell line	P388	Mus musculus	IC50	>=	10000	nM	PMID[24735527]
NPT2909	Organism	Shigella flexneri	Shigella flexneri	MIC	>	150000	nM	PMID[24735527]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	150000	nM	PMID[24735527]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	150000	nM	PMID[24735527]
NPT327	Organism	Microsporum gypseum	Microsporum gypseum	MIC	>	150000	nM	PMID[24735527]
NPT329	Organism	Trichophyton rubrum	Trichophyton rubrum	MIC	>	150000	nM	PMID[24735527]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	150000	nM	PMID[24735527]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	150000	nM	PMID[24735527]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	150000	nM	PMID[24735527]
NPT1533	Organism	Saccharomyces	Saccharomyces	MIC	>	150000	nM	PMID[24735527]
NPT1277	Organism	Staphylococcus epidermidis ATCC 12228	Staphylococcus epidermidis ATCC 12228	MIC	>	150000	nM	PMID[24735527]
NPT2	Others	Unspecified	n.a.	MIC	>	150000	nM	PMID[24735527]

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 NPC476949 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	18656
0.1-0.2	25089
0.2-0.3	5562
0.3-0.4	450
0.4-0.5	70
0.5-0.6	17
0.6-0.7	5
0.7-0.8	1
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
0.7826	Intermediate Similarity	NPC470428
0.7358	Intermediate Similarity	NPC191521
0.717	Intermediate Similarity	NPC159763
0.717	Intermediate Similarity	NPC278386
0.717	Intermediate Similarity	NPC124512
0.7037	Intermediate Similarity	NPC72845
0.6333	Remote Similarity	NPC73911
0.6182	Remote Similarity	NPC131813
0.6182	Remote Similarity	NPC104560
0.6182	Remote Similarity	NPC139692
0.6038	Remote Similarity	NPC474433
0.5893	Remote Similarity	NPC77001
0.5893	Remote Similarity	NPC253618
0.5862	Remote Similarity	NPC242848
0.566	Remote Similarity	NPC175334
0.5614	Remote Similarity	NPC478375
0.5577	Remote Similarity	NPC470429
0.5472	Remote Similarity	NPC91858
0.5455	Remote Similarity	NPC99321
0.5439	Remote Similarity	NPC476602
0.5357	Remote Similarity	NPC79945
0.5254	Remote Similarity	NPC152778
0.5254	Remote Similarity	NPC205034
0.5192	Remote Similarity	NPC149680
0.5192	Remote Similarity	NPC600344
0.5185	Remote Similarity	NPC477924
0.5167	Remote Similarity	NPC474440
0.5082	Remote Similarity	NPC16967

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476949 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6907
0.1-0.2	2128
0.2-0.3	110
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.717	Intermediate Similarity	NPD4225	Phase 3

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