NPASS Compound

Natural Product: NPC18804

Natural Product ID	NPC18804
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(9R,10R)-8,8-Dimethyl-9-[(E)-2-Methylbut-2-Enoyl]Oxy-2-Oxo-9,10-Dihydropyrano[2,3-F]Chromen-10-Yl] (E)-2-Methylbut-2-Enoate
IUPAC Name	[(9R,10R)-8,8-dimethyl-9-[(E)-2-methylbut-2-enoyl]oxy-2-oxo-9,10-dihydropyrano[2,3-f]chromen-10-yl] (E)-2-methylbut-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL71951
PubChem CID	5319252
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0003484] Pyranocoumarins [CHEMONTID:0003485] Angular pyranocoumarins

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 57 59 0 0 0 0 0 0 0 0999 V2000 -3.7265 -4.7879 -0.2448 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2281 -3.6691 0.6203 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3524 -2.7828 0.1839 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8568 -2.9094 -1.2020 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8949 -1.7129 1.0537 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3114 -1.5898 2.2474 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9736 -0.7490 0.6506 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5153 0.2829 1.4494 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8637 1.6584 0.9268 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2093 2.7218 1.5723 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5035 3.9906 1.1003 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3852 4.2055 0.0596 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0134 3.1463 -0.5555 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9043 3.2709 -1.5970 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5079 2.1596 -2.1783 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1711 0.9200 -1.6603 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6699 -0.1339 -2.1264 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3250 0.8381 -0.6748 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7379 1.8574 -0.1031 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6538 2.4376 2.6020 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5184 1.3444 2.5196 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5832 0.7317 3.9134 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8698 1.9148 2.1368 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0051 0.3275 1.5679 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6368 0.3095 0.3271 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3674 -0.7541 -0.1398 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4311 -1.7317 0.6401 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0289 -0.7875 -1.4244 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9743 0.2315 -2.2604 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6527 0.2057 -3.5857 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7948 -1.9847 -1.8375 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0056 -5.0097 -1.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7543 -4.5721 -0.6108 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8330 -5.6875 0.4126 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5732 -3.5502 1.6416 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0958 -2.1451 -1.4546 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6366 -2.8797 -1.9637 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3150 -3.8960 -1.2895 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9817 0.2369 2.4511 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0069 4.8213 1.5902 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5839 5.2107 -0.2748 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1226 4.2658 -1.9522 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1983 2.2566 -2.9855 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3869 1.4869 4.7003 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8581 -0.0929 4.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6081 0.2821 4.0364 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0494 1.9198 1.0550 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9645 2.9689 2.4786 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6336 1.3450 2.7081 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2420 -0.6648 2.0217 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4188 1.1034 -1.9637 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7529 0.2974 -3.4811 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4799 -0.7766 -4.1030 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3101 1.0305 -4.2387 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2385 -2.6300 -2.5430 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0162 -2.5936 -0.9405 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7817 -1.6888 -2.2602 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 10 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 28 31 1 0 24 8 1 0 19 9 1 0 19 13 2 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 0 4 36 1 0 4 37 1 0 4 38 1 0 8 39 1 1 11 40 1 0 12 41 1 0 14 42 1 0 15 43 1 0 22 44 1 0 22 45 1 0 22 46 1 0 23 47 1 0 23 48 1 0 23 49 1 0 24 50 1 1 29 51 1 0 30 52 1 0 30 53 1 0 30 54 1 0 31 55 1 0 31 56 1 0 31 57 1 0 M END

Standard InCHIKey	PNTWXEIQXBRCPS-JLTIQLCOSA-N
Standard InCHI	InChI=1S/C24H26O7/c1-7-13(3)22(26)29-20-18-16(11-9-15-10-12-17(25)28-19(15)18)31-24(5,6)21(20)30-23(27)14(4)8-2/h7-12,20-21H,1-6H3/b13-7+,14-8+/t20-,21-/m1/s1
SMILES	C/C=C(C)/C(=O)O[C@@H]1c2c(ccc3ccc(=O)oc23)OC(C)(C)[C@@H]1OC(=O)/C(=C/C)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	426.17	Volume:	435.794 ? Van der Waals volume.
Dense:	0.978	LogP:	3.402 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.318 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.457 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	92.04 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.407	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.932	Fsp³:	0.375
MCE-18:	73.182 ? 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:	0.849	Fluc inhibitor:	0.143 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.816 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.669 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.329	Promiscuous compounds:	0.104

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.976	MDCK Permeability:	-4.75
Pgp-inhibitor:	0.048	Pgp-substrate:	0.0
PAMPA:	0.705 ? 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):	0.001
20% Bioavailability (F20%):	0.858	30% Bioavailability (F30%):	0.662
50% Bioavailability (F50%):	0.85

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	1.0
Plasma Protein Binding (PPB):	98.262%	Volume Distribution (VD):	0.204
Fu:	1.506% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.133	CYP2C19-substrate:	0.994
CYP2C9-inhibitor:	0.578	CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.844	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.997 ? 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):

6.215

Half-life (T1/2):

0.617

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.274
Human Hepatotoxicity (H-HT):	0.673	Drug-induced Liver Injury (DILI):	0.974
AMES Toxicity:	0.751	Rat Oral Acute Toxicity:	0.682
Maximum Recommended Daily Dose:	0.743	Skin Sensitization:	0.929
Carcinogencity:	0.824	Eye Corrosion:	0.124
Eye Irritation:	0.736	Respiratory Toxicity:	0.744
Drug-induced Neurotoxicity:	0.299	Ototoxicity:	0.255
Hematotoxicity:	0.442	Drug-induced Nephrotoxicity:	0.705
Genotoxicity:	0.984	RPMI-8226 Immunitoxicity:	0.142
A549 Cytotoxicity:	0.18	Hek293 Cytotoxicity:	0.401
BCF:	1.526 ? 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:	4.389 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.306 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.806 ? 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
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	roots	Miyazaki prefecture, Japan	n.a.	PMID[9873511]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3509	Angelica furcijuga	Species	Apiaceae	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
IC50	2
Inhibition	1

Activity Type	# Activity
Organism	3

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
NPT32	Organism	Mus musculus	Mus musculus	IC50	=	3400.0	nM	PMID[9873511]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	IC50	>	100000.0	nM	PMID[9873511]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Inhibition	=	2.8	%	PMID[9873511]

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 NPC18804 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	14267
0.1-0.2	34147
0.2-0.3	1231
0.3-0.4	129
0.4-0.5	42
0.5-0.6	8
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
0.85-0.9	2
0.9-0.95	6
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC84894
1.0	High Similarity	NPC164269
1.0	High Similarity	NPC287182
0.9492	High Similarity	NPC195343
0.9492	High Similarity	NPC267412
0.9492	High Similarity	NPC74655
0.9333	High Similarity	NPC319859
0.9333	High Similarity	NPC198381
0.9333	High Similarity	NPC127888
0.8889	High Similarity	NPC471625
0.875	High Similarity	NPC100986
0.8485	Intermediate Similarity	NPC471630
0.8	Intermediate Similarity	NPC167111
0.8	Intermediate Similarity	NPC318400
0.7937	Intermediate Similarity	NPC166672
0.7692	Intermediate Similarity	NPC471910
0.7576	Intermediate Similarity	NPC296624
0.75	Intermediate Similarity	NPC476457
0.7424	Intermediate Similarity	NPC149320
0.7424	Intermediate Similarity	NPC160727
0.7424	Intermediate Similarity	NPC177281
0.7385	Intermediate Similarity	NPC86892
0.7385	Intermediate Similarity	NPC471909
0.7313	Intermediate Similarity	NPC128529
0.7313	Intermediate Similarity	NPC55615
0.7059	Intermediate Similarity	NPC476455
0.7042	Intermediate Similarity	NPC283019
0.6812	Remote Similarity	NPC307412
0.6812	Remote Similarity	NPC606124
0.6522	Remote Similarity	NPC195357
0.6522	Remote Similarity	NPC152771
0.6471	Remote Similarity	NPC260265
0.6429	Remote Similarity	NPC312881
0.6	Remote Similarity	NPC199204
0.5417	Remote Similarity	NPC469675
0.5342	Remote Similarity	NPC55149
0.5139	Remote Similarity	NPC472424
0.5139	Remote Similarity	NPC281241
0.5135	Remote Similarity	NPC287286
0.5132	Remote Similarity	NPC47163
0.507	Remote Similarity	NPC153818
0.507	Remote Similarity	NPC232246

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC18804 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3378
0.1-0.2	5734
0.2-0.3	38
0.3-0.4	0
0.4-0.5	0
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