NPASS Compound

Natural Product: NPC322465

Natural Product ID	NPC322465
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RNPDONJEBKWTIQ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5316083
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 53 55 0 0 0 0 0 0 0 0999 V2000 -4.2765 -0.9909 -0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1840 0.0338 -0.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2973 1.1022 -1.0451 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1519 2.0601 -0.8282 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9041 1.3120 -1.0832 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6483 0.1557 -0.1239 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8678 -0.6720 0.0643 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9274 -1.9542 -0.7322 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7242 -2.7653 -0.1838 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4273 -2.0201 -0.7671 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3378 -2.7234 -1.4025 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5575 -0.5522 -0.6727 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8525 -0.2629 -0.0256 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3619 1.1320 -0.0505 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6830 1.1198 0.6788 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3090 0.1269 1.2402 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5748 0.5976 1.8336 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6325 1.9654 1.5663 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4900 2.3134 0.8618 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1849 3.4810 0.4387 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6931 -0.0040 1.2676 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3900 0.8071 1.2238 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6483 0.5969 1.3272 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1639 -1.3778 -1.3862 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2175 -0.3605 -0.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4456 -1.7123 0.4211 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2768 1.5784 -0.9460 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2045 0.6913 -2.0656 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1970 2.6216 0.0996 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2377 2.8226 -1.6568 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9952 0.8496 -2.1111 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0652 2.0005 -1.1445 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8332 -1.0441 1.1473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7944 -2.5342 -0.4301 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8099 -1.8130 -1.8071 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8242 -3.7838 -0.5447 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7619 -2.6656 0.9144 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2705 -3.8161 -1.5082 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1830 -2.2146 -1.8531 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7197 -0.2495 -1.7656 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6331 -0.8343 -0.5772 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9493 -0.7375 1.0059 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7872 1.9278 0.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6696 1.3406 -1.1220 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9635 -0.9045 1.2755 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6335 0.4093 2.9259 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5866 -0.2602 0.3374 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5166 0.5025 1.7294 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2008 0.5495 1.9783 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4179 1.9134 1.1934 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2823 1.6234 1.5041 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7695 0.7231 1.2390 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4993 -0.1045 2.1502 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 17 21 1 0 6 22 1 0 2 23 1 0 7 2 1 0 12 6 1 0 19 15 1 0 1 24 1 0 1 25 1 0 1 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 4 30 1 0 5 31 1 0 5 32 1 0 7 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 11 38 1 0 11 39 1 0 12 40 1 0 13 41 1 0 13 42 1 0 14 43 1 0 14 44 1 0 16 45 1 0 17 46 1 0 21 47 1 0 22 48 1 0 22 49 1 0 22 50 1 0 23 51 1 0 23 52 1 0 23 53 1 0 M END

Standard InCHIKey	RNPDONJEBKWTIQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H30O3/c1-13-6-9-16-19(2,3)10-5-11-20(16,4)15(13)8-7-14-12-17(21)23-18(14)22/h12,15-17,21H,1,5-11H2,2-4H3
SMILES	CC1(CCCC2(C1CCC(=C)C2CCC3=CC(OC3=O)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.22	Volume:	347.268 ? Van der Waals volume.
Dense:	0.916	LogP:	3.718 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.592 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.797 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.621	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.365	Fsp³:	0.75
MCE-18:	54.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.041	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:	0.083 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.54	Promiscuous compounds:	0.018

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.581	MDCK Permeability:	-4.838
Pgp-inhibitor:	0.081	Pgp-substrate:	0.0
PAMPA:	0.024 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.227

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.966	MRP1:	0.957
Plasma Protein Binding (PPB):	97.7%	Volume Distribution (VD):	0.101
Fu:	3.092% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.027
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.0
BSEP inhibitor:	0.849

ADMET: Metabolism

CYP1A2-inhibitor:	0.01	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.938	CYP2C19-substrate:	0.208
CYP2C9-inhibitor:	0.058	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.401	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.099	CYP3A4-substrate:	0.515
CYP2B6-substrate:	0.228	CYP2C8-inhibitor:	0.491
HLM stability:	0.954 ? 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):

5.998

Half-life (T1/2):

0.725

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.702
Human Hepatotoxicity (H-HT):	0.593	Drug-induced Liver Injury (DILI):	0.236
AMES Toxicity:	0.15	Rat Oral Acute Toxicity:	0.192
Maximum Recommended Daily Dose:	0.819	Skin Sensitization:	0.976
Carcinogencity:	0.501	Eye Corrosion:	0.075
Eye Irritation:	0.809	Respiratory Toxicity:	0.569
Drug-induced Neurotoxicity:	0.819	Ototoxicity:	0.788
Hematotoxicity:	0.3	Drug-induced Nephrotoxicity:	0.641
Genotoxicity:	0.022	RPMI-8226 Immunitoxicity:	0.062
A549 Cytotoxicity:	0.256	Hek293 Cytotoxicity:	0.22
BCF:	1.869 ? 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:	4.993 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.698 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.28 ? 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
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[21106458]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37514241]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39317685]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25518	Hedychium coronarium	Species	Zingiberaceae	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

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

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 NPC322465 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	15334
0.1-0.2	29006
0.2-0.3	4910
0.3-0.4	473
0.4-0.5	87
0.5-0.6	29
0.6-0.7	12
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC251528
0.717	Intermediate Similarity	NPC475709
0.6792	Remote Similarity	NPC217394
0.6296	Remote Similarity	NPC106416
0.6296	Remote Similarity	NPC86316
0.6296	Remote Similarity	NPC609165
0.625	Remote Similarity	NPC472809
0.625	Remote Similarity	NPC472810
0.6226	Remote Similarity	NPC478390
0.6154	Remote Similarity	NPC185587
0.6071	Remote Similarity	NPC79027
0.6038	Remote Similarity	NPC35655
0.6	Remote Similarity	NPC12170
0.6	Remote Similarity	NPC477783
0.5932	Remote Similarity	NPC489288
0.5882	Remote Similarity	NPC226997
0.5769	Remote Similarity	NPC68703
0.5741	Remote Similarity	NPC484731
0.5741	Remote Similarity	NPC175334
0.569	Remote Similarity	NPC469
0.569	Remote Similarity	NPC478393
0.569	Remote Similarity	NPC177037
0.569	Remote Similarity	NPC472814
0.5686	Remote Similarity	NPC41160
0.5686	Remote Similarity	NPC67840
0.5536	Remote Similarity	NPC99321
0.55	Remote Similarity	NPC478394
0.5439	Remote Similarity	NPC478392
0.5439	Remote Similarity	NPC144947
0.5424	Remote Similarity	NPC311070
0.5345	Remote Similarity	NPC200513
0.5273	Remote Similarity	NPC169275
0.5273	Remote Similarity	NPC52449
0.5179	Remote Similarity	NPC189745
0.5172	Remote Similarity	NPC16321
0.5172	Remote Similarity	NPC608380
0.5167	Remote Similarity	NPC489285
0.5161	Remote Similarity	NPC489287
0.5161	Remote Similarity	NPC485191
0.5094	Remote Similarity	NPC481631
0.5091	Remote Similarity	NPC107258
0.5091	Remote Similarity	NPC481628
0.5085	Remote Similarity	NPC238146

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC322465 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6419
0.1-0.2	2599
0.2-0.3	128
0.3-0.4	0
0.4-0.5	3
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	Drug ID	Developmental Stage
0.5345	Remote Similarity	NPD4752	Clinical (unspecified phase)

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