NPASS Compound

Natural Product: NPC488435

Natural Product ID	NPC488435
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KTMZXANPFHMTFM-YHLNPCLLSA-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]

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 72 74 0 0 0 0 0 0 0 0999 V2000 -3.7163 3.4145 -1.6932 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6135 3.2954 -0.5043 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1657 2.8364 0.6520 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7724 2.4097 0.8708 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6373 0.9726 1.2655 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1668 0.0642 0.2162 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3363 -0.8157 -0.3583 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8305 -1.7320 -1.4055 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7137 -3.1383 -0.9700 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3773 -3.6896 -0.6698 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6380 -5.1761 -0.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4920 -3.8120 -1.8465 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7680 -3.4618 -1.7908 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4038 -2.9238 -0.5909 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5873 -2.7906 0.5104 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1836 -2.2826 1.6643 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5187 -1.9339 1.6947 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3309 -2.0696 0.5873 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7528 -1.6964 0.6251 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6364 -2.5514 0.9564 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1637 -0.3404 0.2825 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2679 0.5587 -0.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5690 1.9395 -0.4230 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8444 2.4390 -0.4362 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0603 3.7724 -0.7919 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0259 4.6165 -1.1349 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7500 4.0894 -1.1140 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5352 2.7737 -0.7632 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3104 5.9247 -1.4766 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7394 -2.5721 -0.5516 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5198 -2.7241 -1.6852 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1049 -1.4254 2.8580 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2901 -1.2783 4.0042 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7393 -3.1436 0.4562 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5665 0.0591 -0.2189 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0333 3.6996 -0.6241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3015 2.4376 -1.9919 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2652 3.8660 -2.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8392 4.0366 -1.3845 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8514 2.7666 1.5097 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2727 3.0469 1.6420 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1498 2.5378 -0.0618 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1987 0.8225 2.2155 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5726 0.7578 1.4857 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3244 -0.8104 -0.0308 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8787 -1.4763 -1.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2226 -1.5015 -2.3177 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2341 -3.7671 -1.7561 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3572 -3.3359 -0.0565 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2456 -5.2031 0.6687 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6827 -5.6786 -0.0401 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1937 -5.6933 -1.0642 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9146 -4.1995 -2.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4419 -3.5510 -2.6578 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5425 -2.1761 2.5364 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2051 -0.0690 0.3106 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2247 0.2004 -0.0661 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6956 1.8164 -0.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0794 4.1320 -0.7913 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9228 4.7534 -1.3852 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5243 2.3728 -0.7514 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1248 6.1810 -2.0167 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2090 -3.4771 -1.7472 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7732 -0.6774 4.7920 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0360 -2.2794 4.4476 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3362 -0.7522 3.7611 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0243 -0.9774 -0.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1893 0.6364 0.5200 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7442 0.4927 -1.2084 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5181 3.2724 -1.5327 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6218 3.3719 0.2474 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0767 4.8167 -0.7402 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 26 29 1 0 18 30 2 0 30 31 1 0 17 32 1 0 32 33 1 0 15 34 1 0 6 35 1 0 2 36 1 0 34 10 1 0 30 14 1 0 28 23 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 7 45 1 0 8 46 1 0 8 47 1 0 9 48 1 0 9 49 1 0 11 50 1 0 11 51 1 0 11 52 1 0 12 53 1 0 13 54 1 0 16 55 1 0 21 56 1 0 22 57 1 0 24 58 1 0 25 59 1 0 27 60 1 0 28 61 1 0 29 62 1 0 31 63 1 0 33 64 1 0 33 65 1 0 33 66 1 0 35 67 1 0 35 68 1 0 35 69 1 0 36 70 1 0 36 71 1 0 36 72 1 0 M END

Standard InCHIKey	KTMZXANPFHMTFM-YHLNPCLLSA-N
Standard InCHI	InChI=1S/C31H36O5/c1-21(2)8-6-9-22(3)10-7-18-31(4)19-17-25-27(36-31)20-28(35-5)29(30(25)34)26(33)16-13-23-11-14-24(32)15-12-23/h8,10-17,19-20,32,34H,6-7,9,18H2,1-5H3/b16-13+,22-10+
SMILES	CC(=CCC/C(=C/CCC1(C)C=Cc2c(cc(c(C(=O)/C=C/c3ccc(cc3)O)c2O)OC)O1)/C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	488.26	Volume:	534.013 ? Van der Waals volume.
Dense:	0.914	LogP:	7.208 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.451 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.16 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	21.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.204	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.638	Fsp³:	0.323
MCE-18:	67.073 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.992 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.642 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.983 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.504	Promiscuous compounds:	0.181

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.958	MDCK Permeability:	-4.715
Pgp-inhibitor:	1.0	Pgp-substrate:	0.0
PAMPA:	0.001 ? 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%):	0.397	30% Bioavailability (F30%):	0.591
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.198
Plasma Protein Binding (PPB):	98.491%	Volume Distribution (VD):	0.106
Fu:	1.318% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.192
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.022	CYP2C19-substrate:	0.998
CYP2C9-inhibitor:	0.801	CYP2C9-substrate:	0.983
CYP2D6-inhibitor:	0.954	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

7.178

Half-life (T1/2):

0.792

ADMET: Toxicity

hERG Blockers:	0.376	hERG Blockers (10um):	0.676
Human Hepatotoxicity (H-HT):	0.726	Drug-induced Liver Injury (DILI):	0.183
AMES Toxicity:	0.175	Rat Oral Acute Toxicity:	0.111
Maximum Recommended Daily Dose:	0.463	Skin Sensitization:	0.968
Carcinogencity:	0.161	Eye Corrosion:	0.002
Eye Irritation:	0.884	Respiratory Toxicity:	0.826
Drug-induced Neurotoxicity:	0.607	Ototoxicity:	0.412
Hematotoxicity:	0.188	Drug-induced Nephrotoxicity:	0.388
Genotoxicity:	0.131	RPMI-8226 Immunitoxicity:	0.11
A549 Cytotoxicity:	0.371	Hek293 Cytotoxicity:	0.597
BCF:	1.929 ? 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:	5.505 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.195 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.744 ? 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
NPO40539	Amomum tsao-ko	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15165158]
NPO40539	Amomum tsao-ko	Species	Zingiberaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[31244142]
NPO40539	Amomum tsao-ko	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
IC50	1

Activity Type	# Activity
Cell line	1

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	IC50	=	30600.0	nM	PMID[31244142]

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 NPC488435 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	16513
0.1-0.2	28381
0.2-0.3	4377
0.3-0.4	455
0.4-0.5	102
0.5-0.6	25
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8636	High Similarity	NPC488436
0.7059	Intermediate Similarity	NPC483636
0.6818	Remote Similarity	NPC226636
0.5926	Remote Similarity	NPC488431
0.5926	Remote Similarity	NPC488432
0.5867	Remote Similarity	NPC477242
0.5857	Remote Similarity	NPC476006
0.5714	Remote Similarity	NPC11561
0.5714	Remote Similarity	NPC284080
0.5634	Remote Similarity	NPC85895
0.5616	Remote Similarity	NPC166138
0.56	Remote Similarity	NPC274109
0.5571	Remote Similarity	NPC41461
0.5488	Remote Similarity	NPC488550
0.5479	Remote Similarity	NPC263384
0.5455	Remote Similarity	NPC477243
0.5443	Remote Similarity	NPC472633
0.5405	Remote Similarity	NPC478288
0.5366	Remote Similarity	NPC474162
0.5357	Remote Similarity	NPC472625
0.5309	Remote Similarity	NPC488549
0.5185	Remote Similarity	NPC488428
0.5185	Remote Similarity	NPC488427
0.5139	Remote Similarity	NPC156590
0.5135	Remote Similarity	NPC74137
0.5128	Remote Similarity	NPC37139
0.5128	Remote Similarity	NPC607595
0.5062	Remote Similarity	NPC476981

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488435 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3856
0.1-0.2	5216
0.2-0.3	75
0.3-0.4	2
0.4-0.5	1
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