NPASS Compound

Natural Product: NPC75049

Natural Product ID	NPC75049
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6,8-Di(Gamma,Gamma-Dimethylallyl)-4',7-Dihydroxyflavanone
IUPAC Name	(2S)-7-hydroxy-2-(4-hydroxyphenyl)-6,8-bis(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL560504
PubChem CID	45267937
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 57 59 0 0 0 0 0 0 0 0999 V2000 -4.9990 -3.7735 0.0832 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6521 -3.0612 -1.1783 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2491 -1.8031 -1.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1159 -1.0453 0.1727 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6979 -0.6088 0.3009 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8544 -1.2430 1.1442 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5447 -0.8492 1.2689 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3712 -1.5513 2.1777 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0539 -2.1551 3.1702 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7970 -1.5060 1.8594 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2263 -0.1067 1.4539 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5676 -0.2572 0.8189 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1663 0.7543 0.1002 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4228 0.6332 -0.4890 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1014 -0.5575 -0.3463 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5388 -1.5999 0.3670 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2832 -1.4281 0.9349 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3745 -0.7165 -0.9288 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3002 0.5829 0.6892 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0090 0.2200 0.5406 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8845 0.8557 -0.3135 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4429 2.0326 -1.0994 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5060 3.2543 -0.2596 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4494 4.0844 0.0365 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1779 5.2775 0.9143 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8261 3.9247 -0.4545 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1951 0.4543 -0.4340 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1040 1.0821 -1.2954 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7747 -3.7851 -2.4630 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0657 -3.9289 0.6297 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5030 -4.7312 -0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7289 -3.1145 0.6189 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9932 -1.2715 -2.0083 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3460 -1.6951 1.0470 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7708 -0.1473 0.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2047 -2.0746 1.7398 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9680 -2.1953 0.9943 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3774 -1.7996 2.7518 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4158 0.4314 2.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6398 1.6813 -0.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8603 1.4634 -1.0500 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1113 -2.5198 0.4525 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9111 -2.2898 1.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1627 -0.8652 -0.3375 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1445 2.1223 -1.9746 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5645 1.8748 -1.5431 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5069 3.4968 0.1764 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9197 6.0800 0.7543 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8179 5.7130 0.6275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0939 4.9566 1.9703 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1622 4.9618 -0.7576 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4800 3.6803 0.4214 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9651 3.2641 -1.3053 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7181 1.7595 -0.8231 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9747 -4.8554 -2.2625 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8054 -3.7762 -3.0441 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5713 -3.3293 -3.0994 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 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 15 18 1 0 11 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 3 24 25 1 0 24 26 1 0 21 27 2 0 27 28 1 0 2 29 1 0 27 5 1 0 20 7 2 0 17 12 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 6 36 1 0 10 37 1 0 10 38 1 0 11 39 1 1 13 40 1 0 14 41 1 0 16 42 1 0 17 43 1 0 18 44 1 0 22 45 1 0 22 46 1 0 23 47 1 0 25 48 1 0 25 49 1 0 25 50 1 0 26 51 1 0 26 52 1 0 26 53 1 0 28 54 1 0 29 55 1 0 29 56 1 0 29 57 1 0 M END

Standard InCHIKey	MLXUEMGNSDHQTJ-QHCPKHFHSA-N
Standard InCHI	InChI=1S/C25H28O4/c1-15(2)5-7-18-13-21-22(27)14-23(17-8-10-19(26)11-9-17)29-25(21)20(24(18)28)12-6-16(3)4/h5-6,8-11,13,23,26,28H,7,12,14H2,1-4H3/t23-/m0/s1
SMILES	CC(=CCc1cc2C(=O)C[C@@H](c3ccc(cc3)O)Oc2c(CC=C(C)C)c1O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	392.2	Volume:	426.719 ? Van der Waals volume.
Dense:	0.919	LogP:	5.686 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.114 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.1 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.629	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.407	Fsp³:	0.32
MCE-18:	62.424 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.992	Fluc inhibitor:	0.86 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.607 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.4 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.493	Promiscuous compounds:	0.059

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.872	MDCK Permeability:	-4.705
Pgp-inhibitor:	0.74	Pgp-substrate:	0.127
PAMPA:	0.393 ? 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):	0.003
20% Bioavailability (F20%):	0.986	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.969
Plasma Protein Binding (PPB):	94.752%	Volume Distribution (VD):	0.278
Fu:	5.281% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.366
OATP1B3 inhibitor:	0.802	BCRP inhibitor:	1.0
BSEP inhibitor:	0.707

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.615	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.147	CYP2D6-substrate:	0.19
CYP3A4-inhibitor:	0.0	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):

10.809

Half-life (T1/2):

1.164

ADMET: Toxicity

hERG Blockers:	0.119	hERG Blockers (10um):	0.524
Human Hepatotoxicity (H-HT):	0.878	Drug-induced Liver Injury (DILI):	0.55
AMES Toxicity:	0.702	Rat Oral Acute Toxicity:	0.932
Maximum Recommended Daily Dose:	0.858	Skin Sensitization:	0.981
Carcinogencity:	0.27	Eye Corrosion:	0.0
Eye Irritation:	0.662	Respiratory Toxicity:	0.951
Drug-induced Neurotoxicity:	0.944	Ototoxicity:	0.709
Hematotoxicity:	0.284	Drug-induced Nephrotoxicity:	0.932
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.092
A549 Cytotoxicity:	0.805	Hek293 Cytotoxicity:	0.685
BCF:	1.894 ? 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:	5.345 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.876 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.418 ? 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
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13293	Lespedeza floribunda	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
FC	1
IC50	1

Activity Type	# Activity
Individual protein	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3143	Individual protein	Solute carrier family 2, facilitated glucose transporter member 4	Rattus norvegicus	FC	=	1.35	n.a.	PMID[28236591]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	2520.0	nM	PMID[22037378]

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 NPC75049 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	17508
0.1-0.2	27234
0.2-0.3	4312
0.3-0.4	590
0.4-0.5	140
0.5-0.6	41
0.6-0.7	21
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8393	Intermediate Similarity	NPC197252
0.807	Intermediate Similarity	NPC310130
0.7544	Intermediate Similarity	NPC164980
0.7119	Intermediate Similarity	NPC236766
0.7	Intermediate Similarity	NPC265040
0.6833	Remote Similarity	NPC150408
0.6833	Remote Similarity	NPC39329
0.6833	Remote Similarity	NPC51032
0.6765	Remote Similarity	NPC160821
0.6613	Remote Similarity	NPC35567
0.6557	Remote Similarity	NPC107572
0.6557	Remote Similarity	NPC32739
0.6462	Remote Similarity	NPC473078
0.6393	Remote Similarity	NPC143896
0.6393	Remote Similarity	NPC169591
0.6393	Remote Similarity	NPC298223
0.6393	Remote Similarity	NPC604412
0.6364	Remote Similarity	NPC36275
0.629	Remote Similarity	NPC91560
0.6269	Remote Similarity	NPC246948
0.625	Remote Similarity	NPC76338
0.625	Remote Similarity	NPC250242
0.619	Remote Similarity	NPC149026
0.619	Remote Similarity	NPC69674
0.6154	Remote Similarity	NPC608140
0.6	Remote Similarity	NPC479215
0.5942	Remote Similarity	NPC479211
0.5938	Remote Similarity	NPC221432
0.5938	Remote Similarity	NPC257097
0.5909	Remote Similarity	NPC293286
0.5857	Remote Similarity	NPC479213
0.5846	Remote Similarity	NPC66515
0.5846	Remote Similarity	NPC220998
0.5846	Remote Similarity	NPC610133
0.5758	Remote Similarity	NPC285555
0.5694	Remote Similarity	NPC479212
0.5634	Remote Similarity	NPC477957
0.5606	Remote Similarity	NPC68104
0.5571	Remote Similarity	NPC166934
0.5571	Remote Similarity	NPC142405
0.5556	Remote Similarity	NPC477958
0.5541	Remote Similarity	NPC132592
0.5538	Remote Similarity	NPC324436
0.5538	Remote Similarity	NPC78
0.5493	Remote Similarity	NPC479214
0.5455	Remote Similarity	NPC187282
0.5455	Remote Similarity	NPC250214
0.5405	Remote Similarity	NPC101793
0.5405	Remote Similarity	NPC609256
0.5397	Remote Similarity	NPC246648
0.5385	Remote Similarity	NPC76372
0.5385	Remote Similarity	NPC37496
0.5385	Remote Similarity	NPC258630
0.5373	Remote Similarity	NPC109223
0.5373	Remote Similarity	NPC10937
0.5352	Remote Similarity	NPC39752
0.5342	Remote Similarity	NPC214774
0.5286	Remote Similarity	NPC291508
0.5224	Remote Similarity	NPC148757
0.5147	Remote Similarity	NPC609848
0.5143	Remote Similarity	NPC161506
0.5132	Remote Similarity	NPC312273
0.5085	Remote Similarity	NPC329225
0.5085	Remote Similarity	NPC147686
0.5082	Remote Similarity	NPC98115
0.5072	Remote Similarity	NPC125855
0.5067	Remote Similarity	NPC479217

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC75049 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3123
0.1-0.2	5849
0.2-0.3	169
0.3-0.4	6
0.4-0.5	2
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
0.5085	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