NPASS Compound

Natural Product: NPC300988

Natural Product ID	NPC300988
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(-)-(2S)-5,7,2'-Trihydroxy-5'-(1''',1'''-Dimethylallyl)-8-Prenylflavanone
IUPAC Name	(2S)-5,7-dihydroxy-2-[2-hydroxy-5-(2-methylbut-3-en-2-yl)phenyl]-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1689201
PubChem CID	51040684
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003642] 8-prenylated flavans [CHEMONTID:0003508] 8-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 58 60 0 0 0 0 0 0 0 0999 V2000 4.3637 -0.8250 -2.8256 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6558 0.0059 -1.8378 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9962 -0.4716 -0.4767 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9688 -1.6200 -0.4980 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6920 0.6716 0.2486 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7371 -0.8529 0.2194 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6042 -2.0118 0.9401 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4062 -2.3042 1.5659 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3564 -1.4352 1.4636 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4389 -0.2584 0.7516 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6408 0.0077 0.1395 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3116 0.6818 0.6396 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4382 1.6722 1.8026 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6799 2.6430 1.6563 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5623 3.8738 1.6339 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0150 2.0573 1.5309 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1720 2.7730 1.8372 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4187 2.1995 1.7113 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4867 0.8949 1.2728 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3432 0.1621 0.9614 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4399 -1.2265 0.5238 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8710 -1.4853 -0.8482 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2104 -0.7357 -1.8407 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2645 0.7455 -1.8740 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6147 -1.4253 -3.1538 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0810 0.7529 1.0923 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9486 0.0150 0.7799 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6959 0.2261 1.1127 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9834 4.0760 2.2685 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1308 -1.7068 2.0882 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3762 -1.9009 -2.6212 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1174 -0.4874 -3.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6352 1.0783 -2.0713 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5361 -2.4736 -1.0486 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2417 -1.9103 0.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9110 -1.3352 -1.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7850 0.5739 0.1815 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4137 1.6327 -0.2344 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4150 0.6865 1.3324 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4393 -2.7044 1.0214 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3304 -3.2170 2.1226 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7673 0.9143 -0.4329 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3514 1.2960 -0.2822 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3014 1.0870 2.7370 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4152 2.1420 1.8423 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2757 2.7669 1.9508 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0125 -1.8548 1.2691 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3931 -1.6797 0.5952 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9106 -2.5963 -1.0747 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2017 1.1697 -1.4574 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2317 1.1009 -2.9383 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3784 1.1463 -1.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1595 -0.8112 -3.9563 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7160 -1.4531 -3.2432 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1286 -2.4066 -3.1866 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2160 -0.1819 1.8707 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9657 4.8117 1.5478 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4006 -2.4938 1.7376 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 3 5 1 0 3 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 3 23 24 1 0 23 25 1 0 20 26 2 0 26 27 1 0 19 28 1 0 17 29 1 0 9 30 1 0 11 6 1 0 27 12 1 0 26 16 1 0 1 31 1 0 1 32 1 0 2 33 1 0 4 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 5 39 1 0 7 40 1 0 8 41 1 0 11 42 1 0 12 43 1 6 13 44 1 0 13 45 1 0 18 46 1 0 21 47 1 0 21 48 1 0 22 49 1 0 24 50 1 0 24 51 1 0 24 52 1 0 25 53 1 0 25 54 1 0 25 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 M END

Standard InCHIKey	XTXBYTLPTUGDBR-QFIPXVFZSA-N
Standard InCHI	InChI=1S/C25H28O5/c1-6-25(4,5)15-8-10-18(26)17(11-15)22-13-21(29)23-20(28)12-19(27)16(24(23)30-22)9-7-14(2)3/h6-8,10-12,22,26-28H,1,9,13H2,2-5H3/t22-/m0/s1
SMILES	C=CC(C)(C)c1ccc(c(c1)[C@@H]1CC(=O)c2c(cc(c(CC=C(C)C)c2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	408.19	Volume:	435.51 ? Van der Waals volume.
Dense:	0.937	LogP:	4.892 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.766 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.328 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.57	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.685	Fsp³:	0.32
MCE-18:	71.788 ? 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:	0.988	Fluc inhibitor:	0.826 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.318 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.803 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.403	Promiscuous compounds:	0.188

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.929	MDCK Permeability:	-4.723
Pgp-inhibitor:	0.968	Pgp-substrate:	0.026
PAMPA:	0.037 ? 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):	0.056
20% Bioavailability (F20%):	0.993	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.947
Plasma Protein Binding (PPB):	95.081%	Volume Distribution (VD):	0.417
Fu:	5.038% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.999
BSEP inhibitor:	0.927

ADMET: Metabolism

CYP1A2-inhibitor:	0.122	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.945	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.106	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.022	CYP2D6-substrate:	0.783
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

3.774

Half-life (T1/2):

1.48

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.614
Human Hepatotoxicity (H-HT):	0.548	Drug-induced Liver Injury (DILI):	0.632
AMES Toxicity:	0.519	Rat Oral Acute Toxicity:	0.91
Maximum Recommended Daily Dose:	0.895	Skin Sensitization:	0.968
Carcinogencity:	0.304	Eye Corrosion:	0.003
Eye Irritation:	0.932	Respiratory Toxicity:	0.99
Drug-induced Neurotoxicity:	0.771	Ototoxicity:	0.67
Hematotoxicity:	0.087	Drug-induced Nephrotoxicity:	0.673
Genotoxicity:	0.965	RPMI-8226 Immunitoxicity:	0.196
A549 Cytotoxicity:	0.97	Hek293 Cytotoxicity:	0.813
BCF:	2.08 ? 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:	4.875 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.539 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.838 ? 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
NPO29456	Theobroma grandiflorum	Species	Malvaceae	Eukaryota	n.a.	seed	n.a.	PMID[14640528]
NPO28901	Blighia sapida	Species	Sapindaceae	Eukaryota	n.a.	fruit	n.a.	PMID[19653254]
NPO28901	Blighia sapida	Species	Sapindaceae	Eukaryota	n.a.	fruit	n.a.	PMID[19653254f]
NPO29014	Dalea boliviana	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[21226489]
NPO29456	Theobroma grandiflorum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29014	Dalea boliviana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28882	Misopates orontium	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28901	Blighia sapida	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29456	Theobroma grandiflorum	Species	Malvaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO29456	Theobroma grandiflorum	Species	Malvaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO28901	Blighia sapida	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29014	Dalea boliviana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28882	Misopates orontium	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28901	Blighia sapida	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29456	Theobroma grandiflorum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29032	Spathiphyllum wallisii	Species	Araceae	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
Inhibition	1
IC5	1

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	82.1	%	PMID[21226489]
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	IC5	=	27.5	uM	PMID[21226489]

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 NPC300988 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	16442
0.1-0.2	29798
0.2-0.3	3150
0.3-0.4	332
0.4-0.5	99
0.5-0.6	22
0.6-0.7	10
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
0.7656	Intermediate Similarity	NPC10990
0.7143	Intermediate Similarity	NPC324436
0.7143	Intermediate Similarity	NPC78
0.7143	Intermediate Similarity	NPC306829
0.6923	Remote Similarity	NPC66515
0.6716	Remote Similarity	NPC182852
0.6615	Remote Similarity	NPC107572
0.6615	Remote Similarity	NPC32739
0.6471	Remote Similarity	NPC485610
0.6462	Remote Similarity	NPC76372
0.6462	Remote Similarity	NPC37496
0.6269	Remote Similarity	NPC148757
0.6143	Remote Similarity	NPC161506
0.6	Remote Similarity	NPC291878
0.5942	Remote Similarity	NPC480990
0.5915	Remote Similarity	NPC36217
0.5753	Remote Similarity	NPC81697
0.5753	Remote Similarity	NPC278249
0.5753	Remote Similarity	NPC223812
0.5753	Remote Similarity	NPC485615
0.5676	Remote Similarity	NPC166934
0.5652	Remote Similarity	NPC91560
0.5634	Remote Similarity	NPC285555
0.5479	Remote Similarity	NPC485620
0.5405	Remote Similarity	NPC85162
0.5342	Remote Similarity	NPC608140
0.5333	Remote Similarity	NPC24136
0.5325	Remote Similarity	NPC485617
0.5211	Remote Similarity	NPC236766
0.5211	Remote Similarity	NPC150408
0.5185	Remote Similarity	NPC218226
0.5135	Remote Similarity	NPC278476
0.507	Remote Similarity	NPC164980
0.5065	Remote Similarity	NPC131568
0.5065	Remote Similarity	NPC131579
0.5065	Remote Similarity	NPC485613

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC300988 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3389
0.1-0.2	5686
0.2-0.3	71
0.3-0.4	4
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