NPASS Compound

Natural Product: NPC322515

Natural Product ID	NPC322515
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QSUSPILNZCEGPK-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	45782956
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids

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 45 46 0 0 0 0 0 0 0 0999 V2000 6.6321 -2.0943 0.7072 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1449 -2.0737 -0.5959 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1760 -1.1776 -1.0053 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6614 -0.2611 -0.0987 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1565 -0.2988 1.1826 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1174 -1.1830 1.6001 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6198 0.7004 -0.5436 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2600 0.0756 -0.3207 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1519 1.0098 -0.7561 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2111 0.4021 -0.5405 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2347 1.4079 -1.0037 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6498 0.8988 -0.8329 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9769 0.5847 0.5959 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3773 0.1002 0.6401 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4371 0.9595 0.8180 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7124 0.4488 0.8496 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9497 -0.9018 0.7073 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9037 -1.7615 0.5304 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6066 -1.2500 0.4972 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0019 1.8276 -2.2951 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2557 2.2488 -0.1779 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3777 -2.8196 0.9308 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5221 -2.7747 -1.3351 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8005 -1.1637 -2.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7496 0.4222 1.8901 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4888 -1.1915 2.6119 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7368 0.9473 -1.6096 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6620 1.6104 0.0823 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1359 -0.1796 0.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2330 -0.8834 -0.8709 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2644 1.1470 -1.8611 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3424 -0.5247 -1.1047 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3836 0.2276 0.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1452 2.2821 -0.2942 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7758 -0.0497 -1.4116 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3555 1.6690 -1.1919 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8125 1.4465 1.2751 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3234 -0.2251 0.9605 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2456 2.0243 0.9298 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5567 1.1224 0.9900 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9692 -1.3117 0.7324 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0277 -2.8298 0.4132 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7654 -1.8989 0.3600 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6973 1.0493 -2.8592 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3153 2.2417 0.7978 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 11 20 1 0 9 21 1 0 6 1 1 0 19 14 1 0 1 22 1 0 2 23 1 0 3 24 1 0 5 25 1 0 6 26 1 0 7 27 1 0 7 28 1 0 8 29 1 0 8 30 1 0 9 31 1 0 10 32 1 0 10 33 1 0 11 34 1 0 12 35 1 0 12 36 1 0 13 37 1 0 13 38 1 0 15 39 1 0 16 40 1 0 17 41 1 0 18 42 1 0 19 43 1 0 20 44 1 0 21 45 1 0 M END

Standard InCHIKey	QSUSPILNZCEGPK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C19H24O2/c20-18(13-11-16-7-3-1-4-8-16)15-19(21)14-12-17-9-5-2-6-10-17/h1-10,18-21H,11-15H2
SMILES	C1=CC=C(C=C1)CCC(CC(CCC2=CC=CC=C2)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.18	Volume:	321.829 ? Van der Waals volume.
Dense:	0.883	LogP:	3.402 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.966 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.407 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	12.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.78	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.489	Fsp³:	0.368
MCE-18:	20.0 ? 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:	0.363	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.079 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.761	Promiscuous compounds:	0.033

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.03	MDCK Permeability:	-4.734
Pgp-inhibitor:	0.997	Pgp-substrate:	0.445
PAMPA:	0.052 ? 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):	0.015
20% Bioavailability (F20%):	0.282	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.031
Plasma Protein Binding (PPB):	95.802%	Volume Distribution (VD):	0.214
Fu:	5.122% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.661
OATP1B3 inhibitor:	0.679	BCRP inhibitor:	0.806
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.04
CYP2C19-inhibitor:	0.881	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.697	CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.238	CYP2D6-substrate:	0.016
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.052
HLM stability:	0.429 ? 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):

11.551

Half-life (T1/2):

0.992

ADMET: Toxicity

hERG Blockers:	0.912	hERG Blockers (10um):	0.95
Human Hepatotoxicity (H-HT):	0.815	Drug-induced Liver Injury (DILI):	0.015
AMES Toxicity:	0.082	Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.804	Skin Sensitization:	0.759
Carcinogencity:	0.051	Eye Corrosion:	0.002
Eye Irritation:	0.199	Respiratory Toxicity:	0.203
Drug-induced Neurotoxicity:	0.412	Ototoxicity:	0.943
Hematotoxicity:	0.179	Drug-induced Nephrotoxicity:	0.955
Genotoxicity:	0.005	RPMI-8226 Immunitoxicity:	0.02
A549 Cytotoxicity:	0.372	Hek293 Cytotoxicity:	0.65
BCF:	1.16 ? 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:	3.626 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.82 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.304 ? 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
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	root	n.a.	PMID[18484537]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[18484537]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[19615910]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29323912]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[731398]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	root	n.a.	PMID[731398]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23911	Alpinia officinarum	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23911	Alpinia officinarum	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

Activity Type	# Activity
Activity	1
Inhibition	1

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
NPT113	Cell line	RAW264.7	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[35576655]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	23.51	%	PMID[35576655]

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 NPC322515 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	29883
0.1-0.2	18508
0.2-0.3	1261
0.3-0.4	138
0.4-0.5	45
0.5-0.6	10
0.6-0.7	7
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	NPC121478
0.7742	Intermediate Similarity	NPC213730
0.6452	Remote Similarity	NPC91461
0.6452	Remote Similarity	NPC7686
0.6452	Remote Similarity	NPC40258
0.6389	Remote Similarity	NPC99482
0.6	Remote Similarity	NPC187725
0.6	Remote Similarity	NPC141607
0.6	Remote Similarity	NPC310194
0.5882	Remote Similarity	NPC474272
0.5854	Remote Similarity	NPC324571
0.5588	Remote Similarity	NPC187583
0.5526	Remote Similarity	NPC164449
0.5526	Remote Similarity	NPC184030
0.5517	Remote Similarity	NPC208302
0.5405	Remote Similarity	NPC179002
0.5405	Remote Similarity	NPC257430
0.5185	Remote Similarity	NPC212114
0.5122	Remote Similarity	NPC249435

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC322515 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4830
0.1-0.2	3948
0.2-0.3	341
0.3-0.4	28
0.4-0.5	3
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