NPASS Compound

Natural Product: NPC303686

Natural Product ID	NPC303686
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WCYYIFXENZTEHA-WCHZOBDOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000050] Lactones [CHEMONTID:0001245] Gamma butyrolactones

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 0.7673 -3.4547 -0.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0590 -2.5189 0.3259 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5102 -2.7545 0.2495 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3067 -1.6456 0.8881 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8085 -0.2811 0.6144 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7789 0.5772 -0.1578 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4279 -0.0466 -1.3206 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8544 1.0268 0.8452 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0755 1.8433 -0.5821 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0609 2.2531 0.4227 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0781 1.2434 0.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3801 -0.1664 0.1262 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1886 -0.4587 -1.3333 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4003 -1.2049 0.8993 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8687 -1.1743 0.7476 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5751 0.0169 1.2527 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3347 0.8140 0.5296 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5924 0.6270 -0.9121 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9734 2.0270 -1.3543 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5519 2.6560 -0.2064 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0714 2.0048 0.9200 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2630 2.4117 2.0918 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7069 -0.2334 -1.0084 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3726 -4.4008 -0.5153 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8395 -3.3944 -0.0976 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7098 -3.7112 0.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8554 -2.9597 -0.8051 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3702 -1.7893 0.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3675 -1.9020 1.9846 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7529 0.2375 1.6267 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1502 0.4883 -2.2771 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5399 0.1529 -1.2609 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3581 -1.1418 -1.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3696 1.1060 1.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2059 2.0478 0.5875 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6826 0.2919 0.8847 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5739 1.6710 -1.5516 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8128 2.6653 -0.7809 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4577 2.3660 1.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6242 3.2383 0.1653 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6170 1.3959 1.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7521 1.5927 -0.4364 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0806 -0.6398 -1.9174 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4634 -1.3699 -1.4924 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3894 0.3492 -1.8532 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0563 -1.2154 1.9597 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1214 -1.4001 -0.3118 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3012 -2.0401 1.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4782 0.2752 2.3051 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7493 0.2066 -1.4584 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6974 1.9206 -2.1753 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0829 2.5415 -1.7151 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2581 -0.1441 -0.1988 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 12 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 18 23 1 0 14 2 1 0 21 17 1 0 12 5 1 0 1 24 1 0 1 25 1 0 3 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 1 7 31 1 0 7 32 1 0 7 33 1 0 8 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 13 43 1 0 13 44 1 0 13 45 1 0 14 46 1 1 15 47 1 0 15 48 1 0 16 49 1 0 18 50 1 0 19 51 1 0 19 52 1 0 23 53 1 0 M END

Standard InCHIKey	WCYYIFXENZTEHA-WCHZOBDOSA-N
Standard InCHI	InChI=1S/C20H30O3/c1-13-6-9-17-19(2,3)10-5-11-20(17,4)15(13)8-7-14-16(21)12-23-18(14)22/h7,15-17,21H,1,5-6,8-12H2,2-4H3/b14-7+/t15-,16?,17-,20+/m1/s1
SMILES	C=C1CC[C@@H]2C(C)(C)CCC[C@@]2(C)[C@@H]1C/C=C/1C(COC1=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.22	Volume:	347.268 ? Van der Waals volume.
Dense:	0.916	LogP:	3.239 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.36 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.314 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	19.0
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:	0.475	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.401	Fsp³:	0.75
MCE-18:	55.2 ? 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:	0.24	Fluc inhibitor:	0.087 ? 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:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.64	Promiscuous compounds:	0.068

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.822	MDCK Permeability:	-4.779
Pgp-inhibitor:	0.971	Pgp-substrate:	0.0
PAMPA:	0.031 ? 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%):	0.024
50% Bioavailability (F50%):	0.111

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.059	MRP1:	0.071
Plasma Protein Binding (PPB):	95.781%	Volume Distribution (VD):	-0.09
Fu:	4.204% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.022
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.451	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.016
CYP2C9-inhibitor:	0.02	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.013	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.984	CYP3A4-substrate:	0.123
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.048
HLM stability:	0.689 ? 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):

7.776

Half-life (T1/2):

0.974

ADMET: Toxicity

hERG Blockers:	0.078	hERG Blockers (10um):	0.338
Human Hepatotoxicity (H-HT):	0.771	Drug-induced Liver Injury (DILI):	0.55
AMES Toxicity:	0.619	Rat Oral Acute Toxicity:	0.613
Maximum Recommended Daily Dose:	0.897	Skin Sensitization:	0.891
Carcinogencity:	0.905	Eye Corrosion:	0.009
Eye Irritation:	0.598	Respiratory Toxicity:	0.605
Drug-induced Neurotoxicity:	0.625	Ototoxicity:	0.713
Hematotoxicity:	0.723	Drug-induced Nephrotoxicity:	0.92
Genotoxicity:	0.817	RPMI-8226 Immunitoxicity:	0.134
A549 Cytotoxicity:	0.452	Hek293 Cytotoxicity:	0.458
BCF:	2.035 ? 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:	4.663 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.09 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.596 ? 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
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12951092]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[12951092]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[15930771]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38999684]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5033	Alpinia galanga	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5033	Alpinia galanga	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 NPC303686 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	15111
0.1-0.2	26237
0.2-0.3	7774
0.3-0.4	575
0.4-0.5	105
0.5-0.6	32
0.6-0.7	19
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	NPC79027
0.6981	Remote Similarity	NPC12170
0.6964	Remote Similarity	NPC159763
0.6964	Remote Similarity	NPC278386
0.6964	Remote Similarity	NPC124512
0.6909	Remote Similarity	NPC177037
0.6909	Remote Similarity	NPC472814
0.6852	Remote Similarity	NPC217394
0.6604	Remote Similarity	NPC478390
0.6481	Remote Similarity	NPC488426
0.6415	Remote Similarity	NPC189745
0.6415	Remote Similarity	NPC175334
0.6316	Remote Similarity	NPC475709
0.6182	Remote Similarity	NPC99321
0.6102	Remote Similarity	NPC478394
0.6071	Remote Similarity	NPC251528
0.6071	Remote Similarity	NPC144947
0.6034	Remote Similarity	NPC311070
0.6034	Remote Similarity	NPC469
0.6034	Remote Similarity	NPC478393
0.5926	Remote Similarity	NPC169275
0.5926	Remote Similarity	NPC52449
0.5818	Remote Similarity	NPC35655
0.5763	Remote Similarity	NPC472809
0.5763	Remote Similarity	NPC472810
0.569	Remote Similarity	NPC238146
0.5593	Remote Similarity	NPC50488
0.5593	Remote Similarity	NPC474396
0.5571	Remote Similarity	NPC264153
0.5536	Remote Similarity	NPC484731
0.5517	Remote Similarity	NPC16321
0.55	Remote Similarity	NPC478375
0.5484	Remote Similarity	NPC489288
0.5484	Remote Similarity	NPC478391
0.5357	Remote Similarity	NPC185587
0.5333	Remote Similarity	NPC75485
0.5333	Remote Similarity	NPC329692
0.5333	Remote Similarity	NPC168975
0.5254	Remote Similarity	NPC106416
0.5254	Remote Similarity	NPC86316
0.5254	Remote Similarity	NPC609165
0.5238	Remote Similarity	NPC72845
0.5185	Remote Similarity	NPC41160
0.5185	Remote Similarity	NPC67840
0.5172	Remote Similarity	NPC4509
0.5152	Remote Similarity	NPC87335
0.5091	Remote Similarity	NPC149680
0.5091	Remote Similarity	NPC226997
0.5091	Remote Similarity	NPC600344
0.5088	Remote Similarity	NPC470428
0.5088	Remote Similarity	NPC484730
0.5088	Remote Similarity	NPC484729

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC303686 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6089
0.1-0.2	2852
0.2-0.3	205
0.3-0.4	0
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6964	Remote Similarity	NPD4225	Phase 3

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