NPASS Compound

Natural Product: NPC29247

Natural Product ID	NPC29247
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FANSVSJYEUVUGE-WOMLPUEGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3233976
PubChem CID	90670217
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003782] Kaurane 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 56 59 0 0 0 0 0 0 0 0999 V2000 -4.1314 -1.1366 1.2292 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3022 -0.1305 0.9308 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4742 0.8584 -0.1655 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1265 0.3110 -1.5250 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6003 0.3458 -1.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0005 -0.1689 -0.4797 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3847 -0.7370 -0.5801 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4478 -2.1750 -0.0829 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8219 -2.7095 0.0243 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9572 -1.8225 0.2381 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7707 -0.3537 0.2492 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5609 0.3790 -0.8084 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3473 0.1994 1.5823 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7126 -0.3293 2.6731 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3339 -0.0112 0.2892 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0774 1.4989 0.2344 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1761 1.7061 1.0519 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2616 0.8461 0.5564 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0612 0.1766 1.6500 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7610 -0.0548 2.8325 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3785 1.8322 0.1707 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7203 2.4917 1.3513 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4629 3.0521 1.1678 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7021 -0.8880 -2.0268 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9531 -1.4192 -2.3140 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6454 1.2264 -2.4656 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9414 -1.8170 2.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0207 -1.2766 0.6412 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4785 1.3178 -0.1471 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5282 -0.6840 -1.7228 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2981 1.3458 -2.0585 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4808 -0.3062 -2.6382 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6335 -1.0999 -0.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1081 -2.1752 0.8805 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1851 -2.8108 -0.7711 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7668 -3.5414 0.7936 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0212 -3.2905 -0.9290 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4328 -2.1262 1.2272 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8427 -2.0272 -0.4484 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2387 -0.2486 -1.3948 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2423 1.1757 -0.3802 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8485 0.9942 -1.4177 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4674 1.2864 1.5566 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4131 -0.1931 1.6208 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7465 0.2828 3.4308 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0488 -0.2692 1.3388 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9679 1.8450 -0.8090 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8702 2.0769 0.6858 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0889 1.3596 2.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1000 2.5192 -0.5988 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6030 2.9105 1.3268 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5772 3.3511 2.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0036 -1.6695 -2.4048 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4926 0.0223 -2.6286 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9710 -2.0803 -3.0171 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4760 2.1412 -2.1090 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 6 11 13 1 0 13 14 1 0 11 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 1 19 20 2 0 18 21 1 0 21 22 1 0 17 23 1 0 7 24 1 6 24 25 1 0 4 26 1 0 19 2 1 0 21 3 1 0 18 6 1 0 15 7 1 0 1 27 1 0 1 28 1 0 3 29 1 6 4 30 1 6 5 31 1 0 5 32 1 0 6 33 1 1 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 12 40 1 0 12 41 1 0 12 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 15 46 1 1 16 47 1 0 16 48 1 0 17 49 1 1 21 50 1 6 22 51 1 0 23 52 1 0 24 53 1 0 24 54 1 0 25 55 1 0 26 56 1 0 M END

Standard InCHIKey	FANSVSJYEUVUGE-WOMLPUEGSA-N
Standard InCHI	InChI=1S/C20H30O6/c1-10-15-11(23)6-13-19(9-22)5-3-4-18(2,8-21)12(19)7-14(24)20(13,16(10)25)17(15)26/h11-15,17,21-24,26H,1,3-9H2,2H3/t11-,12+,13-,14+,15+,17+,18+,19-,20-/m0/s1
SMILES	C=C1[C@@H]2[C@H](C[C@H]3[C@@]4(CCC[C@](C)(CO)[C@H]4C[C@H]([C@@]3(C1=O)[C@@H]2O)O)CO)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	366.2	Volume:	367.719 ? Van der Waals volume.
Dense:	0.996	LogP:	0.658 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.223 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.185 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	21.0
TPSA:	118.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.44	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.349	Fsp³:	0.85
MCE-18:	108.946 ? 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:	0.208	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.037 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.192	Promiscuous compounds:	0.273

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.005	MDCK Permeability:	-5.149
Pgp-inhibitor:	0.003	Pgp-substrate:	0.645
PAMPA:	1.0 ? 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):	0.721
20% Bioavailability (F20%):	0.997	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.081	MRP1:	0.146
Plasma Protein Binding (PPB):	39.149%	Volume Distribution (VD):	-0.145
Fu:	61.94% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.969
OATP1B3 inhibitor:	0.325	BCRP inhibitor:	0.881
BSEP inhibitor:	0.205

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.009	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.039	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.018	CYP2D6-substrate:	0.014
CYP3A4-inhibitor:	0.019	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.21
HLM stability:	0.048 ? 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):

4.089

Half-life (T1/2):

2.108

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.057
Human Hepatotoxicity (H-HT):	0.831	Drug-induced Liver Injury (DILI):	0.49
AMES Toxicity:	0.891	Rat Oral Acute Toxicity:	0.401
Maximum Recommended Daily Dose:	0.436	Skin Sensitization:	0.997
Carcinogencity:	0.859	Eye Corrosion:	0.0
Eye Irritation:	0.365	Respiratory Toxicity:	0.568
Drug-induced Neurotoxicity:	0.063	Ototoxicity:	0.849
Hematotoxicity:	0.932	Drug-induced Nephrotoxicity:	0.984
Genotoxicity:	0.925	RPMI-8226 Immunitoxicity:	0.294
A549 Cytotoxicity:	0.683	Hek293 Cytotoxicity:	0.588
BCF:	0.431 ? 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:	3.079 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.667 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.663 ? 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
NPO15942	Isodon wikstroemioides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24697496]
NPO15942	Isodon wikstroemioides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15942	Isodon wikstroemioides	Species	Lamiaceae	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
IC50	5

Activity Type	# Activity
Cell line	5

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	>	10000.0	nM	PubChem BioAssay data set
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	>	10000.0	nM	PMID[1965654]
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[21982797]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[26052978]
NPT660	Cell line	SW480	Homo sapiens	IC50	>	10000.0	nM	PMID[24063539]

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 NPC29247 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	17237
0.1-0.2	29805
0.2-0.3	2654
0.3-0.4	109
0.4-0.5	29
0.5-0.6	12
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8636	High Similarity	NPC104371
0.8	Intermediate Similarity	NPC91772
0.6875	Remote Similarity	NPC299185
0.6667	Remote Similarity	NPC129004
0.64	Remote Similarity	NPC261333
0.64	Remote Similarity	NPC135548
0.64	Remote Similarity	NPC215271
0.6154	Remote Similarity	NPC156324
0.6	Remote Similarity	NPC153775
0.6	Remote Similarity	NPC101233
0.6	Remote Similarity	NPC289539
0.5769	Remote Similarity	NPC149761
0.5714	Remote Similarity	NPC88203
0.5577	Remote Similarity	NPC292374
0.5472	Remote Similarity	NPC231060
0.5472	Remote Similarity	NPC259009
0.537	Remote Similarity	NPC84018
0.5283	Remote Similarity	NPC127408
0.5273	Remote Similarity	NPC41070
0.5273	Remote Similarity	NPC64006
0.5091	Remote Similarity	NPC55503
0.5088	Remote Similarity	NPC76866
0.5085	Remote Similarity	NPC287676

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC29247 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5918
0.1-0.2	3186
0.2-0.3	46
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