NPASS Compound

Natural Product: NPC77484

Natural Product ID	NPC77484
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KBHVJOKVQQUHTM-HWKANZROSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	15118819
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 47 48 0 0 0 0 0 0 0 0999 V2000 6.0423 0.6399 2.7016 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6544 1.0745 1.5011 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0853 0.6587 0.3047 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9666 -0.1470 0.2529 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4264 -0.5419 -0.9462 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2218 -1.4090 -0.9276 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0172 -0.4948 -0.9279 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7444 -1.2758 -0.9098 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7714 -2.5339 -0.8967 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5508 -0.6056 -0.9068 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6933 -1.2609 -0.8910 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0170 -0.5394 -0.8883 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7083 -0.9853 0.4015 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0390 -0.3464 0.5394 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1789 -0.9335 0.0328 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4176 -0.3393 0.1609 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5563 0.8637 0.8010 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4180 1.4604 1.3126 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1776 0.8659 1.1847 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5309 2.6921 1.9727 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8038 1.4978 0.9496 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9780 -0.1508 -2.1404 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1040 0.6601 -2.0983 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6368 1.0498 -0.8904 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7652 1.8622 -0.8801 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0082 -0.4814 2.6392 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0246 1.0436 2.7460 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6652 0.8852 3.5859 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5432 -0.4469 1.2118 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2101 -2.0419 -1.8209 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2472 -2.0608 -0.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0246 0.1808 -1.7909 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0456 0.1246 -0.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6237 0.4819 -0.9177 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6660 -2.3414 -0.8796 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6355 -0.8178 -1.7473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8556 0.5504 -0.8006 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7908 -2.0915 0.3494 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0982 -0.7099 1.2652 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1146 -1.8929 -0.4851 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2924 -0.8218 -0.2454 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2855 1.3569 1.5985 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3067 2.8675 2.6163 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9866 2.2365 0.2535 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5489 -0.4644 -3.0825 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5315 0.9631 -3.0592 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4839 1.7188 -1.5748 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 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 18 20 1 0 17 21 1 0 5 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 24 3 1 0 19 14 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 6 30 1 0 6 31 1 0 7 32 1 0 7 33 1 0 10 34 1 0 11 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 15 40 1 0 16 41 1 0 19 42 1 0 20 43 1 0 21 44 1 0 22 45 1 0 23 46 1 0 25 47 1 0 M END

Standard InCHIKey	KBHVJOKVQQUHTM-HWKANZROSA-N
Standard InCHI	InChI=1S/C20H22O5/c1-25-20-13-15(8-11-18(20)23)6-9-16(21)5-3-2-4-14-7-10-17(22)19(24)12-14/h3,5,7-8,10-13,22-24H,2,4,6,9H2,1H3/b5-3+
SMILES	COc1cc(CCC(=O)/C=C/CCc2ccc(c(c2)O)O)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	342.15	Volume:	360.223 ? Van der Waals volume.
Dense:	0.95	LogP:	2.506 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.687 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.799 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	14.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.505	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.409	Fsp³:	0.25
MCE-18:	13.0 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.517	Fluc inhibitor:	0.2 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.023 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.408 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.67	Promiscuous compounds:	0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.051	MDCK Permeability:	-4.77
Pgp-inhibitor:	0.925	Pgp-substrate:	0.007
PAMPA:	0.006 ? 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):	0.003
20% Bioavailability (F20%):	0.83	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.01
Plasma Protein Binding (PPB):	97.665%	Volume Distribution (VD):	-0.612
Fu:	2.073% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.102
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.977	CYP1A2-substrate:	0.649
CYP2C19-inhibitor:	0.929	CYP2C19-substrate:	0.944
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.034
CYP2D6-inhibitor:	0.974	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.815
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.971 ? 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):

12.312

Half-life (T1/2):

1.383

ADMET: Toxicity

hERG Blockers:	0.549	hERG Blockers (10um):	0.89
Human Hepatotoxicity (H-HT):	0.712	Drug-induced Liver Injury (DILI):	0.148
AMES Toxicity:	0.586	Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.692	Skin Sensitization:	0.999
Carcinogencity:	0.141	Eye Corrosion:	0.009
Eye Irritation:	0.883	Respiratory Toxicity:	0.676
Drug-induced Neurotoxicity:	0.065	Ototoxicity:	0.695
Hematotoxicity:	0.094	Drug-induced Nephrotoxicity:	0.184
Genotoxicity:	0.602	RPMI-8226 Immunitoxicity:	0.039
A549 Cytotoxicity:	0.807	Hek293 Cytotoxicity:	0.653
BCF:	1.651 ? 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:	4.566 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.58 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.256 ? 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

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 NPC77484 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	20535
0.1-0.2	22996
0.2-0.3	5511
0.3-0.4	658
0.4-0.5	100
0.5-0.6	31
0.6-0.7	12
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8889	High Similarity	NPC5018
0.8163	Intermediate Similarity	NPC123228
0.8163	Intermediate Similarity	NPC123722
0.8	Intermediate Similarity	NPC179777
0.7556	Intermediate Similarity	NPC61062
0.72	Intermediate Similarity	NPC114298
0.7059	Intermediate Similarity	NPC4181
0.6809	Remote Similarity	NPC299406
0.6792	Remote Similarity	NPC164778
0.6667	Remote Similarity	NPC257976
0.6667	Remote Similarity	NPC273686
0.6667	Remote Similarity	NPC242372
0.6667	Remote Similarity	NPC312404
0.6545	Remote Similarity	NPC231572
0.6491	Remote Similarity	NPC65935
0.6491	Remote Similarity	NPC319282
0.62	Remote Similarity	NPC127937
0.6111	Remote Similarity	NPC343720
0.6111	Remote Similarity	NPC54872
0.5965	Remote Similarity	NPC276466
0.5918	Remote Similarity	NPC29989
0.5818	Remote Similarity	NPC303680
0.5741	Remote Similarity	NPC481914
0.5636	Remote Similarity	NPC53305
0.5625	Remote Similarity	NPC8547
0.5536	Remote Similarity	NPC201777
0.5536	Remote Similarity	NPC604524
0.5472	Remote Similarity	NPC49529
0.5472	Remote Similarity	NPC56214
0.5472	Remote Similarity	NPC602856
0.5439	Remote Similarity	NPC137427
0.5417	Remote Similarity	NPC257124
0.5345	Remote Similarity	NPC481913
0.5345	Remote Similarity	NPC163083
0.5333	Remote Similarity	NPC304622
0.5319	Remote Similarity	NPC156840
0.5283	Remote Similarity	NPC177291
0.5254	Remote Similarity	NPC257589
0.5246	Remote Similarity	NPC84076
0.5246	Remote Similarity	NPC151167
0.5192	Remote Similarity	NPC17943
0.5167	Remote Similarity	NPC229497
0.5088	Remote Similarity	NPC297657
0.5088	Remote Similarity	NPC159968
0.5082	Remote Similarity	NPC20287
0.5082	Remote Similarity	NPC215941
0.5082	Remote Similarity	NPC123196
0.5082	Remote Similarity	NPC20404
0.5082	Remote Similarity	NPC311419
0.5079	Remote Similarity	NPC90128

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC77484 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3571
0.1-0.2	5267
0.2-0.3	291
0.3-0.4	18
0.4-0.5	2
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
0.5417	Remote Similarity	NPD228	Phase 0

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