NPASS Compound

Natural Product: NPC253344

Natural Product ID	NPC253344
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KXZKYCRWMZGOMF-NEDXIOEJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	6324843
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 70 71 0 0 0 0 0 0 0 0999 V2000 -10.7520 -0.6767 -0.3591 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5075 0.2788 0.8161 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0782 1.6463 0.5036 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9906 0.4506 0.8960 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3209 -0.7919 1.1216 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.0565 -0.8700 0.8879 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2870 0.2761 0.3986 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9697 0.1628 0.1644 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1879 1.2735 -0.3172 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9149 1.2056 -0.5554 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1207 -0.0214 -0.3592 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0474 0.3493 0.6765 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1747 -0.8300 0.9774 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5063 -1.2812 -0.2892 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4188 -2.4695 -0.0346 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0519 -2.8515 -1.3423 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8722 -1.7451 -1.9555 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9991 -1.3026 -1.0742 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7473 -0.1889 -1.8006 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8785 0.2912 -0.9734 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1133 0.2249 -1.3975 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2516 0.6829 -0.6216 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5502 0.5818 -1.1383 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6554 1.0007 -0.4429 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5349 1.5450 0.8078 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2768 1.6643 1.3564 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1558 1.2326 0.6358 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4664 2.2385 2.6053 O 0 0 0 0 0 0 0 0 0 0 0 0 10.7480 2.8828 2.6362 C 0 0 0 0 0 0 0 0 0 0 0 0 11.4715 2.0451 1.7235 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4184 -2.0665 1.1066 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0645 -1.5438 -0.2803 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.7813 -1.0410 -0.3859 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4512 -0.1349 -1.2860 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8944 -0.1422 1.7575 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9150 1.5995 -0.2080 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3612 2.1689 1.4625 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3066 2.3150 0.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7527 1.2282 1.6400 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6962 0.8366 -0.1238 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7190 1.2465 0.2039 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5464 -0.7893 0.3552 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6793 2.2534 -0.5027 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4171 2.1229 -0.9232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7179 -0.8439 0.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6315 -0.2457 -1.3401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4923 0.8274 1.5514 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4059 1.1050 0.1526 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5545 -0.5135 1.7550 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7926 -1.6557 1.4004 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2960 -1.6790 -0.9676 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0562 -0.4348 -0.7026 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2156 -2.2384 0.6944 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8053 -3.3138 0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7004 -3.7250 -1.1534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2284 -3.1063 -2.0414 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3003 -2.1811 -2.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2880 -0.8788 -2.2626 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5872 -0.9306 -0.1223 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7304 -2.1018 -0.8967 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0288 0.6266 -1.9639 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0780 -0.5350 -2.7991 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6670 0.7011 -0.0050 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3121 -0.1967 -2.3896 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6681 0.1604 -2.1121 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6686 0.9239 -0.8415 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1914 1.3446 1.1027 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1856 2.8951 3.6324 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6474 3.8874 2.1659 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8640 -2.9490 1.2258 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 1 0 6 31 1 0 27 22 1 0 30 25 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 0 3 36 1 0 3 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 7 41 1 0 8 42 1 0 9 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 12 48 1 0 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 18 59 1 0 18 60 1 0 19 61 1 0 19 62 1 0 20 63 1 0 21 64 1 0 23 65 1 0 24 66 1 0 27 67 1 0 29 68 1 0 29 69 1 0 31 70 1 0 M END

Standard InCHIKey	KXZKYCRWMZGOMF-NEDXIOEJSA-N
Standard InCHI	InChI=1S/C27H39NO3/c1-23(2)21-28-27(29)17-15-13-11-9-7-5-3-4-6-8-10-12-14-16-24-18-19-25-26(20-24)31-22-30-25/h11,13-20,23H,3-10,12,21-22H2,1-2H3,(H,28,29)/b13-11?,16-14+,17-15+
SMILES	CC(C)CN=C(/C=C/C=CCCCCCCCCC/C=C/c1ccc2c(c1)OCO2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	425.29	Volume:	477.347 ? Van der Waals volume.
Dense:	0.891	LogP:	7.902 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.492 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.79 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	14.0
TPSA:	51.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.136	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.04	Fsp³:	0.519
MCE-18:	22.537 ? 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:	0.999	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.071 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.845 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.196	Promiscuous compounds:	0.114

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.951	MDCK Permeability:	-4.619
Pgp-inhibitor:	0.902	Pgp-substrate:	0.004
PAMPA:	0.003 ? 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%):	0.874	30% Bioavailability (F30%):	0.824
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.015
Plasma Protein Binding (PPB):	99.009%	Volume Distribution (VD):	-0.136
Fu:	0.61% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.182
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.076	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.922
CYP2C9-inhibitor:	0.784	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.983
CYP3A4-inhibitor:	0.044	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.144 ? 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):

4.876

Half-life (T1/2):

0.605

ADMET: Toxicity

hERG Blockers:	0.455	hERG Blockers (10um):	0.423
Human Hepatotoxicity (H-HT):	0.961	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.253
Maximum Recommended Daily Dose:	0.632	Skin Sensitization:	1.0
Carcinogencity:	0.765	Eye Corrosion:	0.007
Eye Irritation:	0.771	Respiratory Toxicity:	0.856
Drug-induced Neurotoxicity:	0.118	Ototoxicity:	0.447
Hematotoxicity:	0.17	Drug-induced Nephrotoxicity:	0.844
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.31	Hek293 Cytotoxicity:	0.609
BCF:	1.587 ? 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:	5.423 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.096 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.602 ? 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]
NPO13358	Piper brachystachyum	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]
NPO13358	Piper brachystachyum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13358	Piper brachystachyum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
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 NPC253344 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	20498
0.1-0.2	27835
0.2-0.3	1378
0.3-0.4	70
0.4-0.5	34
0.5-0.6	26
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	3
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC41331
1.0	High Similarity	NPC291449
0.9821	High Similarity	NPC71105
0.8966	High Similarity	NPC170583
0.8793	High Similarity	NPC156944
0.8621	High Similarity	NPC152186
0.7419	Intermediate Similarity	NPC191302
0.7167	Intermediate Similarity	NPC182147
0.7167	Intermediate Similarity	NPC207541
0.7167	Intermediate Similarity	NPC246133
0.6818	Remote Similarity	NPC147247
0.65	Remote Similarity	NPC300955
0.6212	Remote Similarity	NPC99798
0.6119	Remote Similarity	NPC220923
0.6119	Remote Similarity	NPC196609
0.6061	Remote Similarity	NPC251466
0.597	Remote Similarity	NPC328419
0.5882	Remote Similarity	NPC246974
0.5735	Remote Similarity	NPC114845
0.5672	Remote Similarity	NPC230698
0.5672	Remote Similarity	NPC99078
0.5672	Remote Similarity	NPC96406
0.5588	Remote Similarity	NPC473463
0.5522	Remote Similarity	NPC193673
0.5522	Remote Similarity	NPC157740
0.5507	Remote Similarity	NPC73883
0.5507	Remote Similarity	NPC251454
0.5441	Remote Similarity	NPC318862
0.5373	Remote Similarity	NPC194359
0.5373	Remote Similarity	NPC28641
0.5373	Remote Similarity	NPC180647
0.5373	Remote Similarity	NPC225745
0.5362	Remote Similarity	NPC103947
0.5362	Remote Similarity	NPC45783
0.5352	Remote Similarity	NPC282477
0.5352	Remote Similarity	NPC284855
0.5224	Remote Similarity	NPC69670
0.5172	Remote Similarity	NPC104138
0.5172	Remote Similarity	NPC273023
0.5172	Remote Similarity	NPC24216
0.5172	Remote Similarity	NPC306420
0.5085	Remote Similarity	NPC261158

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC253344 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3111
0.1-0.2	5873
0.2-0.3	159
0.3-0.4	5
0.4-0.5	2
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