NPASS Compound

Natural Product: NPC254694

Natural Product ID	NPC254694
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JFGPNOXTEWMCEU-WFYKWJGLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71665600
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000296] Benzodioxoles

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 64 66 0 0 0 0 0 0 0 0999 V2000 0.4841 -0.1113 0.5975 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9794 -0.4438 0.8953 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7893 0.8004 1.1204 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7912 1.7219 -0.0645 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3530 1.0998 -1.3026 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7798 0.6652 -1.1056 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1301 -0.5793 -1.2452 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4036 -1.2074 -1.1113 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3629 -2.5118 -1.2974 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6689 -0.7368 -0.8263 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.1215 0.6198 -0.6442 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1711 0.8423 0.8605 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8597 -0.3460 1.4803 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6576 -1.1705 0.4994 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7747 -1.7182 -0.6093 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1894 -1.4321 0.3914 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6522 -1.2620 0.0867 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3962 -0.5531 1.1959 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8239 -0.4584 0.7532 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4537 0.6660 0.5953 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8389 0.8136 0.1677 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4064 2.0762 0.0340 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7188 2.2385 -0.3703 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5244 1.1575 -0.6593 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9738 -0.0993 -0.5307 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6453 -0.2632 -0.1214 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9801 -0.9912 -0.8759 O 0 0 0 0 0 0 0 0 0 0 0 0 11.2422 -0.3492 -0.8832 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8488 1.0113 -1.0781 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4956 0.4678 -0.3450 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9001 0.4966 1.3990 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0568 -1.0550 1.8256 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4311 -1.0293 0.0858 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8028 0.5016 1.4041 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3652 1.3786 1.9796 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4089 2.6030 0.1845 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7765 2.0605 -0.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3984 1.8931 -2.0831 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7608 0.2826 -1.7098 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5072 1.3830 -0.8327 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2644 -1.2443 -1.5166 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6322 1.3905 -1.2156 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2357 0.6445 -0.9655 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1126 0.8242 1.2244 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6825 1.7792 1.1202 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1767 -0.9633 2.0903 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6174 0.0572 2.2149 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5218 -0.6212 0.0910 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0442 -2.0429 1.0639 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3563 -1.7175 -1.5383 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3934 -2.7222 -0.4090 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7251 -1.9060 -0.4979 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0254 -2.1170 1.2379 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7592 -0.7370 -0.8800 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0758 -2.2765 -0.0542 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9734 0.4445 1.4119 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2895 -1.1575 2.1203 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3408 -1.3861 0.5598 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8821 1.5773 0.8053 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7624 2.9286 0.2646 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1418 3.2239 -0.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2653 -1.2619 -0.0371 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9040 -0.7062 -1.6878 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6691 -0.4718 0.1308 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 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 1 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 15 10 1 0 26 21 1 0 29 24 1 0 1 30 1 0 1 31 1 0 2 32 1 0 2 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 0 7 41 1 0 11 42 1 0 11 43 1 0 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 14 48 1 0 14 49 1 0 15 50 1 0 15 51 1 0 16 52 1 0 16 53 1 0 17 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 0 20 59 1 0 22 60 1 0 23 61 1 0 26 62 1 0 28 63 1 0 28 64 1 0 M END

Standard InCHIKey	JFGPNOXTEWMCEU-WFYKWJGLSA-N
Standard InCHI	InChI=1S/C25H35NO3/c27-25(26-18-12-9-13-19-26)15-11-8-6-4-2-1-3-5-7-10-14-22-16-17-23-24(20-22)29-21-28-23/h10-11,14-17,20H,1-9,12-13,18-19,21H2/b14-10+,15-11+
SMILES	C(CCCC/C=C/C(=O)N1CCCCC1)CCC/C=C/c1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	397.26	Volume:	436.835 ? Van der Waals volume.
Dense:	0.909	LogP:	5.2 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.448 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.429 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	19.0
TPSA:	38.77 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.334	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.484	Fsp³:	0.56
MCE-18:	32.308 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.945	Fluc inhibitor:	0.997 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.364 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.887 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.018	Promiscuous compounds:	0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.931	MDCK Permeability:	-4.639
Pgp-inhibitor:	0.991	Pgp-substrate:	0.0
PAMPA:	0.0 ? 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):	0.001
20% Bioavailability (F20%):	0.365	30% Bioavailability (F30%):	0.063
50% Bioavailability (F50%):	0.305

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.007
Plasma Protein Binding (PPB):	99.111%	Volume Distribution (VD):	0.133
Fu:	0.58% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.863
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.104
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.341	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.871
CYP2C9-inhibitor:	0.921	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.764 ? 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):

4.855

Half-life (T1/2):

0.496

ADMET: Toxicity

hERG Blockers:	0.635	hERG Blockers (10um):	0.554
Human Hepatotoxicity (H-HT):	0.706	Drug-induced Liver Injury (DILI):	0.241
AMES Toxicity:	0.409	Rat Oral Acute Toxicity:	0.064
Maximum Recommended Daily Dose:	0.732	Skin Sensitization:	0.991
Carcinogencity:	0.226	Eye Corrosion:	0.022
Eye Irritation:	0.767	Respiratory Toxicity:	0.716
Drug-induced Neurotoxicity:	0.286	Ototoxicity:	0.175
Hematotoxicity:	0.167	Drug-induced Nephrotoxicity:	0.406
Genotoxicity:	0.005	RPMI-8226 Immunitoxicity:	0.139
A549 Cytotoxicity:	0.545	Hek293 Cytotoxicity:	0.751
BCF:	1.454 ? 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:	5.114 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.791 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.903 ? 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
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[23506561]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	leaves	n.a.	n.a.	PMID[25127165]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6648	Piper retrofractum	Species	Piperaceae	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 NPC254694 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	21325
0.1-0.2	27010
0.2-0.3	1357
0.3-0.4	104
0.4-0.5	21
0.5-0.6	13
0.6-0.7	9
0.7-0.8	1
0.8-0.85	0
0.85-0.9	4
0.9-0.95	0
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC230698
1.0	High Similarity	NPC99078
1.0	High Similarity	NPC96406
0.9796	High Similarity	NPC193673
0.8824	High Similarity	NPC159150
0.8704	High Similarity	NPC220923
0.8704	High Similarity	NPC196609
0.8519	High Similarity	NPC328419
0.7857	Intermediate Similarity	NPC73883
0.7857	Intermediate Similarity	NPC251454
0.7679	Intermediate Similarity	NPC103947
0.7679	Intermediate Similarity	NPC45783
0.75	Intermediate Similarity	NPC318862
0.7455	Intermediate Similarity	NPC194359
0.7455	Intermediate Similarity	NPC28641
0.7455	Intermediate Similarity	NPC180647
0.7455	Intermediate Similarity	NPC225745
0.7091	Intermediate Similarity	NPC255817
0.7091	Intermediate Similarity	NPC136330
0.6981	Remote Similarity	NPC167096
0.6981	Remote Similarity	NPC605721
0.6909	Remote Similarity	NPC94280
0.6842	Remote Similarity	NPC205178
0.6842	Remote Similarity	NPC227218
0.6792	Remote Similarity	NPC217574
0.6271	Remote Similarity	NPC248505
0.6094	Remote Similarity	NPC270811
0.6094	Remote Similarity	NPC471073
0.5965	Remote Similarity	NPC470707
0.5938	Remote Similarity	NPC156944
0.5932	Remote Similarity	NPC252107
0.5781	Remote Similarity	NPC95366
0.5781	Remote Similarity	NPC152186
0.5672	Remote Similarity	NPC41331
0.5672	Remote Similarity	NPC291449
0.5538	Remote Similarity	NPC191302
0.5522	Remote Similarity	NPC71105
0.5238	Remote Similarity	NPC145446
0.5238	Remote Similarity	NPC137172
0.5082	Remote Similarity	NPC469808
0.5079	Remote Similarity	NPC69670

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC254694 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4328
0.1-0.2	4716
0.2-0.3	97
0.3-0.4	7
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
0.7091	Intermediate Similarity	NPD2492	Phase 2

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