NPASS Compound

Natural Product: NPC209040

Natural Product ID	NPC209040
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-Hydroxy-4'-Methoxy-3'-(3-Hydroxy-3-Methyl-Trans-But-1-Enyl)-5'-(3-Methylbut-2-Enyl)Flavanone
IUPAC Name	(2S)-7-hydroxy-2-[3-[(E)-3-hydroxy-3-methylbut-1-enyl]-4-methoxy-5-(3-methylbut-2-enyl)phenyl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL513212
PubChem CID	11995581
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003643] 3'-prenylated flavans [CHEMONTID:0003506] 3'-prenylated flavanones

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 61 63 0 0 0 0 0 0 0 0999 V2000 -1.9336 -4.9751 2.1482 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4766 -4.3304 0.8645 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0819 -3.2498 0.4041 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6293 -2.6365 -0.8397 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1559 -1.2420 -0.7353 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2151 -1.0082 -0.6937 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7577 0.2376 -0.5932 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1372 1.3003 -0.5317 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4953 1.1452 -0.5674 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3989 2.2779 -0.5005 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0106 3.5138 -0.4035 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0232 4.6110 -0.3412 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5388 4.7691 1.0944 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1753 4.2449 -1.2377 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4873 5.8342 -0.6987 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9859 -0.1616 -0.6716 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3576 -0.2881 -0.7066 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2258 -0.4182 0.3703 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2172 0.5060 -0.5476 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7422 0.4141 -1.9456 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1019 -0.1929 -2.0048 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6018 -0.5932 -3.0941 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9198 -0.3544 -0.8141 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3056 -0.4251 -0.8274 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0384 -0.5783 0.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3998 -0.6659 1.5407 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0021 -0.5941 1.5498 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2694 -0.4423 0.4082 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8852 -0.3638 0.3465 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0708 -0.8215 2.7522 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3156 -4.9493 0.1275 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4179 -5.9452 2.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0205 -5.1925 2.1031 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6498 -4.3153 2.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8998 -2.8456 0.9590 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8014 -3.2674 -1.2755 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4303 -2.7038 -1.6429 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8926 -1.8555 -0.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2905 2.2822 -0.4522 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4704 2.0893 -0.5331 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9911 3.7934 -0.3652 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3224 5.5519 1.0372 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9065 3.8189 1.5037 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6823 5.1844 1.6829 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6611 5.1439 -1.6643 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8917 3.6011 -0.6700 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7666 3.5981 -2.0509 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1028 6.2915 0.1116 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8162 -1.3662 0.2108 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6425 -0.5258 1.2946 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9909 0.3839 0.4307 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3846 1.5457 -0.1815 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8059 1.3882 -2.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0955 -0.2436 -2.5875 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7795 -0.3523 -1.8036 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1104 -0.6293 0.2858 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4860 -0.6601 2.4844 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6736 -0.0705 3.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6879 -5.2567 -0.8700 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0593 -5.8212 0.7029 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4760 -4.1849 0.0064 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 12 14 1 0 12 15 1 0 9 16 2 0 16 17 1 0 17 18 1 0 7 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 26 30 1 0 2 31 1 0 16 5 1 0 29 19 1 0 28 23 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 6 38 1 0 8 39 1 0 10 40 1 0 11 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 14 47 1 0 15 48 1 0 18 49 1 0 18 50 1 0 18 51 1 0 19 52 1 1 20 53 1 0 20 54 1 0 24 55 1 0 25 56 1 0 27 57 1 0 30 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 M END

Standard InCHIKey	SRFNFECUBWLUHV-YSESTWPTSA-N
Standard InCHI	InChI=1S/C26H30O5/c1-16(2)6-7-17-12-19(13-18(25(17)30-5)10-11-26(3,4)29)23-15-22(28)21-9-8-20(27)14-24(21)31-23/h6,8-14,23,27,29H,7,15H2,1-5H3/b11-10+/t23-/m0/s1
SMILES	CC(=CCc1cc(cc(/C=C/C(C)(C)O)c1OC)[C@@H]1CC(=O)c2ccc(cc2O1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.21	Volume:	452.806 ? Van der Waals volume.
Dense:	0.932	LogP:	4.948 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.854 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.441 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	20.0
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:	0.61	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.586	Fsp³:	0.346
MCE-18:	68.514 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.94	Fluc inhibitor:	0.903 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.216 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.529 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.222	Promiscuous compounds:	0.203

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.834	MDCK Permeability:	-4.756
Pgp-inhibitor:	0.761	Pgp-substrate:	0.012
PAMPA:	0.104 ? 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):	0.002
20% Bioavailability (F20%):	0.488	30% Bioavailability (F30%):	0.959
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.583
Plasma Protein Binding (PPB):	94.91%	Volume Distribution (VD):	0.095
Fu:	3.978% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.91
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.995
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.192	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.822	CYP2C19-substrate:	0.995
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.894	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

8.018

Half-life (T1/2):

1.26

ADMET: Toxicity

hERG Blockers:	0.236	hERG Blockers (10um):	0.489
Human Hepatotoxicity (H-HT):	0.911	Drug-induced Liver Injury (DILI):	0.75
AMES Toxicity:	0.822	Rat Oral Acute Toxicity:	0.817
Maximum Recommended Daily Dose:	0.932	Skin Sensitization:	0.827
Carcinogencity:	0.75	Eye Corrosion:	0.0
Eye Irritation:	0.205	Respiratory Toxicity:	0.855
Drug-induced Neurotoxicity:	0.837	Ototoxicity:	0.76
Hematotoxicity:	0.395	Drug-induced Nephrotoxicity:	0.935
Genotoxicity:	0.995	RPMI-8226 Immunitoxicity:	0.143
A549 Cytotoxicity:	0.794	Hek293 Cytotoxicity:	0.773
BCF:	1.772 ? 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:	4.614 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.096 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.573 ? 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
NPO27739	Erythrina mildbraedii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0031-9422(88)80746-5]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	root barks	n.a.	n.a.	PMID[15689169]
NPO27739	Erythrina mildbraedii	Species	Fabaceae	Eukaryota	root bark	Buea, Southwest Province, Cameroon	1997-JUL	PMID[17125223]
NPO27459	Balanophora tobiracola	Species	Balanophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22444	Ceramium boydenii	Species	Ceramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27739	Erythrina mildbraedii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22444	Ceramium boydenii	Species	Ceramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27459	Balanophora tobiracola	Species	Balanophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27739	Erythrina mildbraedii	Species	Fabaceae	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	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	>	60000.0	nM	PMID[17125223]

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 NPC209040 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	15367
0.1-0.2	29151
0.2-0.3	4613
0.3-0.4	570
0.4-0.5	120
0.5-0.6	23
0.6-0.7	8
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	Natural Product ID
0.7969	Intermediate Similarity	NPC68104
0.7606	Intermediate Similarity	NPC214166
0.75	Intermediate Similarity	NPC110303
0.75	Intermediate Similarity	NPC601247
0.6716	Remote Similarity	NPC143896
0.6522	Remote Similarity	NPC221432
0.6522	Remote Similarity	NPC257097
0.6447	Remote Similarity	NPC227579
0.6301	Remote Similarity	NPC291508
0.6	Remote Similarity	NPC169591
0.6	Remote Similarity	NPC298223
0.6	Remote Similarity	NPC604412
0.5972	Remote Similarity	NPC17170
0.575	Remote Similarity	NPC111786
0.5694	Remote Similarity	NPC39329
0.5694	Remote Similarity	NPC51032
0.5679	Remote Similarity	NPC132592
0.5538	Remote Similarity	NPC329225
0.5538	Remote Similarity	NPC147686
0.5526	Remote Similarity	NPC23728
0.5522	Remote Similarity	NPC264083
0.5441	Remote Similarity	NPC1612
0.5441	Remote Similarity	NPC183959
0.5395	Remote Similarity	NPC474033
0.5375	Remote Similarity	NPC477957
0.5309	Remote Similarity	NPC477958
0.525	Remote Similarity	NPC474021
0.5147	Remote Similarity	NPC476480
0.5147	Remote Similarity	NPC84585
0.5135	Remote Similarity	NPC164980
0.5132	Remote Similarity	NPC109223
0.5132	Remote Similarity	NPC220998
0.5132	Remote Similarity	NPC10937
0.5065	Remote Similarity	NPC76338
0.5065	Remote Similarity	NPC250242

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC209040 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3165
0.1-0.2	5888
0.2-0.3	90
0.3-0.4	5
0.4-0.5	1
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
0.5538	Remote Similarity	NPD1549	Phase 2

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