NPASS Compound

Natural Product: NPC194970

Natural Product ID	NPC194970
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1Beta-P-Coumaroyloxypolygodial
IUPAC Name	[(1R,4aS,8R,8aS)-7,8-diformyl-4,4,8a-trimethyl-1,2,3,4a,5,8-hexahydronaphthalen-1-yl] (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms	1Beta-P-Coumaroyloxypolygodial
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2333577
PubChem CID	14241022
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0003002] Hydroxycinnamic acid esters [CHEMONTID:0000465] Coumaric acid esters

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 57 59 0 0 0 0 0 0 0 0999 V2000 -4.1700 -0.3410 -1.9103 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5633 -1.0995 -0.7478 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7442 -1.8039 -0.0527 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6523 -2.1907 -1.1987 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2024 -1.9058 -1.2035 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7611 -1.0768 -0.0370 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5517 0.2213 0.0006 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4379 0.9775 -1.2986 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0426 1.1103 1.0811 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5892 2.4332 0.5591 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5538 2.7663 0.7203 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9808 1.4166 2.1846 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2886 1.3539 2.0309 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8090 0.9581 0.6942 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9590 -0.2137 0.2953 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4118 1.8049 3.5002 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1746 2.0673 4.4447 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6116 -0.8839 0.0541 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4267 -1.2995 1.0676 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9324 -1.9134 2.0196 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8634 -0.9944 0.9764 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3710 -0.3423 -0.0392 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7690 -0.0201 -0.1740 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6941 -0.3749 0.7618 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0476 -0.0547 0.6174 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4628 0.6334 -0.4904 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5601 1.0125 -1.4630 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2451 0.6801 -1.2843 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7888 0.9791 -0.6894 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2463 -0.6335 -2.0923 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6690 -0.5705 -2.8765 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2288 0.7584 -1.7111 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6067 -1.1424 0.0461 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0475 -2.6455 -0.7075 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3562 -2.2063 0.8925 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9531 -2.4468 -2.2579 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8401 -3.1545 -0.6403 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8744 -1.5168 -2.1865 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6551 -2.8924 -1.1060 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0636 -1.6360 0.8769 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5838 0.3895 -2.1986 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1208 1.8222 -1.3087 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3960 1.4116 -1.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1240 0.6195 1.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2687 3.0834 0.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9725 1.5790 2.8368 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7028 1.8313 0.0411 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8658 0.6705 0.7203 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8826 -0.8637 1.2210 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3563 1.8551 3.6224 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4843 -1.3309 1.7824 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6738 -0.0266 -0.8315 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4045 -0.9219 1.6553 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7394 -0.3607 1.3905 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8605 1.5568 -2.3485 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5116 0.9655 -2.0341 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1523 1.9058 -0.5327 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 2 0 9 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 12 16 1 0 16 17 2 0 6 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 26 29 1 0 15 2 1 0 28 23 1 0 15 7 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 3 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 6 40 1 1 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 1 10 45 1 0 13 46 1 0 14 47 1 0 14 48 1 0 15 49 1 1 16 50 1 0 21 51 1 0 22 52 1 0 24 53 1 0 25 54 1 0 27 55 1 0 28 56 1 0 29 57 1 0 M END

Standard InCHIKey	OOBNDBQPMFZTTD-TWEQYNAUSA-N
Standard InCHI	InChI=1S/C24H28O5/c1-23(2)13-12-21(24(3)19(15-26)17(14-25)7-10-20(23)24)29-22(28)11-6-16-4-8-18(27)9-5-16/h4-9,11,14-15,19-21,27H,10,12-13H2,1-3H3/b11-6+/t19-,20-,21+,24+/m0/s1
SMILES	CC1(C)CC[C@H]([C@]2(C)[C@@H](C=O)C(=CC[C@@H]12)C=O)OC(=O)/C=C/c1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	396.19	Volume:	420.85 ? Van der Waals volume.
Dense:	0.941	LogP:	3.634 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.198 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.01 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	80.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.46	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.213	Fsp³:	0.458
MCE-18:	76.057 ? 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:	0.983	Fluc inhibitor:	0.664 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.163 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.346 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.408	Promiscuous compounds:	0.091

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.939	MDCK Permeability:	-4.667
Pgp-inhibitor:	0.938	Pgp-substrate:	0.008
PAMPA:	0.107 ? 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):	0.002
20% Bioavailability (F20%):	0.665	30% Bioavailability (F30%):	0.636
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.011
Plasma Protein Binding (PPB):	96.037%	Volume Distribution (VD):	0.263
Fu:	3.669% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.025
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.848
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.418
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.081
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.029
CYP3A4-inhibitor:	0.905	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.423 ? 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):

6.842

Half-life (T1/2):

1.098

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.306
Human Hepatotoxicity (H-HT):	0.421	Drug-induced Liver Injury (DILI):	0.434
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.371
Maximum Recommended Daily Dose:	0.906	Skin Sensitization:	0.992
Carcinogencity:	0.677	Eye Corrosion:	0.053
Eye Irritation:	0.881	Respiratory Toxicity:	0.416
Drug-induced Neurotoxicity:	0.363	Ototoxicity:	0.121
Hematotoxicity:	0.274	Drug-induced Nephrotoxicity:	0.529
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.134	Hek293 Cytotoxicity:	0.835
BCF:	1.498 ? 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:	4.968 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.676 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.239 ? 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
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10993146]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	Tsukuba, Japan	1998-JUN	PMID[12381108]
NPO19593	Placida dendritica	Species	Limapontiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[14575447]
NPO19593	Placida dendritica	Species	Limapontiidae	Eukaryota	n.a.	Mediterranean	n.a.	PMID[14575447]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24197199]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24254087]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.		PMID[31861466]
NPO5929	Neoscopelus microchir	Species	Neoscopelidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17965	Helenium arizonicum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19593	Placida dendritica	Species	Limapontiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	Oil	n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	Shoot	n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17965	Helenium arizonicum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17965	Helenium arizonicum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19652	Pittosporum phillyraeoides	Species	Pittosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5929	Neoscopelus microchir	Species	Neoscopelidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8589	Triticum aestivum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19593	Placida dendritica	Species	Limapontiidae	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
GI50	2

Activity Type	# Activity
Cell line	2

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
NPT386	Cell line	KM12	Homo sapiens	GI50	=	25000.0	nM	PMID[23517126]
NPT407	Cell line	COLO 205	Homo sapiens	GI50	=	29000.0	nM	PMID[23517126]

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 NPC194970 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	6580
0.1-0.2	37545
0.2-0.3	5205
0.3-0.4	471
0.4-0.5	56
0.5-0.6	1
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	Natural Product ID
0.5278	Remote Similarity	NPC152812

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC194970 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3766
0.1-0.2	5258
0.2-0.3	123
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