NPASS Compound

Natural Product: NPC74924

Natural Product ID	NPC74924
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Propolin B
IUPAC Name	(2S)-2-[3,4-dihydroxy-5-[(E)-7-hydroxy-3,7-dimethyloct-2-enyl]phenyl]-5,7-dihydroxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL468032
PubChem CID	637252
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 62 64 0 0 0 0 0 0 0 0999 V2000 -3.1109 -2.6095 -2.3412 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8128 -1.4848 -1.3820 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5752 -1.0600 -1.2381 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4135 -1.6432 -1.9880 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6027 -2.0855 -0.9912 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7470 -1.3232 -0.7815 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7299 -1.6661 0.1238 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5341 -2.8205 0.8323 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4257 -3.6234 0.6761 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4530 -3.2358 -0.2549 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6614 -4.0473 -0.4091 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2149 -4.7948 1.3869 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8899 -0.7801 0.2529 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6601 -0.9715 1.5384 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7470 0.0614 1.5468 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8819 -0.1671 2.0464 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5201 1.3925 0.9642 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4618 2.3887 1.0312 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2404 3.6381 0.4803 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0385 3.8521 -0.1410 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0985 2.8577 -0.2078 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3112 1.6014 0.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3918 0.5677 0.2982 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7769 5.0813 -0.7029 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6790 2.1721 1.6605 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9144 -0.8665 -0.6055 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3784 0.2176 0.2749 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4456 0.8492 1.0975 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5665 1.5026 0.3908 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4934 2.0793 1.4868 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1887 2.5750 -0.5706 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3757 0.5677 -0.2998 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1959 -2.4875 -2.6203 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5508 -2.5140 -3.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9429 -3.5486 -1.7903 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2822 -0.2443 -0.5599 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0181 -0.8207 -2.6084 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6662 -2.5165 -2.5886 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8340 -0.4245 -1.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2961 -3.1085 1.5507 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4814 -3.8921 0.1701 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3785 -5.6884 0.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5721 -0.9392 -0.5852 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0941 -1.9644 1.6537 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9557 -0.7975 2.3813 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0110 4.4246 0.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1225 2.9860 -0.6956 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0890 5.2004 -1.6798 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3436 1.5756 1.1889 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6478 -0.4245 -1.3439 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4316 -1.6182 0.0455 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5715 -0.2101 0.9422 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8605 0.9414 -0.3913 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8888 0.0813 1.7996 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9312 1.5596 1.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8970 2.7439 2.1339 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8736 1.1791 2.0301 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2837 2.6326 0.9754 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9456 2.1066 -1.5474 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1161 3.1844 -0.7685 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4377 3.2761 -0.2084 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1780 1.0826 -0.5997 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 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 9 12 1 0 7 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 20 24 1 0 18 25 1 0 2 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 29 32 1 0 10 5 1 0 23 13 1 0 22 17 1 0 1 33 1 0 1 34 1 0 1 35 1 0 3 36 1 0 4 37 1 0 4 38 1 0 6 39 1 0 8 40 1 0 11 41 1 0 12 42 1 0 13 43 1 6 14 44 1 0 14 45 1 0 19 46 1 0 21 47 1 0 24 48 1 0 25 49 1 0 26 50 1 0 26 51 1 0 27 52 1 0 27 53 1 0 28 54 1 0 28 55 1 0 30 56 1 0 30 57 1 0 30 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 32 62 1 0 M END

Standard InCHIKey	WCDJIWAYGSJPBT-LDEBPVJWSA-N
Standard InCHI	InChI=1S/C25H30O7/c1-14(5-4-8-25(2,3)31)6-7-15-9-16(10-20(29)24(15)30)21-13-19(28)23-18(27)11-17(26)12-22(23)32-21/h6,9-12,21,26-27,29-31H,4-5,7-8,13H2,1-3H3/b14-6+/t21-/m0/s1
SMILES	C/C(=CCc1cc(cc(c1O)O)[C@@H]1CC(=O)c2c(cc(cc2O1)O)O)/CCCC(C)(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.2	Volume:	455.727 ? Van der Waals volume.
Dense:	0.97	LogP:	4.204 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.209 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.306 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	19.0
TPSA:	127.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.312	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.593	Fsp³:	0.4
MCE-18:	71.629 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.713	Fluc inhibitor:	0.895 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.106 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.628 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.097	Promiscuous compounds:	0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.174	MDCK Permeability:	-4.815
Pgp-inhibitor:	0.093	Pgp-substrate:	0.002
PAMPA:	0.057 ? 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%):	0.207	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.293
Plasma Protein Binding (PPB):	96.878%	Volume Distribution (VD):	-0.222
Fu:	2.562% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.897
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	1.0
BSEP inhibitor:	0.227

ADMET: Metabolism

CYP1A2-inhibitor:	0.88	CYP1A2-substrate:	0.754
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.958
CYP2C9-inhibitor:	0.015	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.992 ? 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):

7.376

Half-life (T1/2):

1.33

ADMET: Toxicity

hERG Blockers:	0.1	hERG Blockers (10um):	0.471
Human Hepatotoxicity (H-HT):	0.921	Drug-induced Liver Injury (DILI):	0.809
AMES Toxicity:	0.588	Rat Oral Acute Toxicity:	0.708
Maximum Recommended Daily Dose:	0.947	Skin Sensitization:	0.981
Carcinogencity:	0.422	Eye Corrosion:	0.0
Eye Irritation:	0.882	Respiratory Toxicity:	0.977
Drug-induced Neurotoxicity:	0.253	Ototoxicity:	0.781
Hematotoxicity:	0.23	Drug-induced Nephrotoxicity:	0.861
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.244
A549 Cytotoxicity:	0.863	Hek293 Cytotoxicity:	0.747
BCF:	1.761 ? 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:	4.515 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.898 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.306 ? 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
NPO33467	taiwanese propolis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[12713401]
NPO33467	taiwanese propolis	Species	n.a.	n.a.	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	4
Activity	4

Activity Type	# Activity
Cell line	3
Others	5

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
NPT76	Cell line	C6	Rattus norvegicus	IC50	=	4.0	ug.mL-1	PMID[22264170]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	7.5	ug.mL-1	PMID[20155971]
NPT3880	Cell line	Melanoma cells	Homo sapiens	IC50	=	7.5	ug.mL-1	PMID[12036363]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	9.0	ug.mL-1	PMID[20155971]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	18.3	%	PMID[17420206]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	36.7	%	PMID[20055495]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	85.7	%	PMID[17420206]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	94.7	%	PMID[24095094]

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 NPC74924 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	16319
0.1-0.2	30038
0.2-0.3	2899
0.3-0.4	464
0.4-0.5	92
0.5-0.6	30
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
0.7846	Intermediate Similarity	NPC106976
0.7067	Intermediate Similarity	NPC24640
0.6528	Remote Similarity	NPC470890
0.6471	Remote Similarity	NPC258630
0.6447	Remote Similarity	NPC261063
0.6197	Remote Similarity	NPC109223
0.6197	Remote Similarity	NPC10937
0.6154	Remote Similarity	NPC298692
0.6104	Remote Similarity	NPC488556
0.6049	Remote Similarity	NPC488555
0.6049	Remote Similarity	NPC484418
0.6027	Remote Similarity	NPC85121
0.5867	Remote Similarity	NPC200761
0.5844	Remote Similarity	NPC474021
0.5844	Remote Similarity	NPC96408
0.5844	Remote Similarity	NPC610511
0.5811	Remote Similarity	NPC174953
0.5802	Remote Similarity	NPC488557
0.5753	Remote Similarity	NPC17170
0.575	Remote Similarity	NPC488558
0.5735	Remote Similarity	NPC321011
0.5735	Remote Similarity	NPC294852
0.5735	Remote Similarity	NPC188679
0.5732	Remote Similarity	NPC484417
0.557	Remote Similarity	NPC279650
0.5556	Remote Similarity	NPC67396
0.5432	Remote Similarity	NPC214166
0.5375	Remote Similarity	NPC470802
0.5373	Remote Similarity	NPC182421
0.5325	Remote Similarity	NPC134783
0.5244	Remote Similarity	NPC58805
0.519	Remote Similarity	NPC473990
0.5125	Remote Similarity	NPC118256
0.5122	Remote Similarity	NPC474038
0.5119	Remote Similarity	NPC474023
0.5072	Remote Similarity	NPC32441
0.5072	Remote Similarity	NPC243083
0.5072	Remote Similarity	NPC13768
0.5072	Remote Similarity	NPC287246
0.5072	Remote Similarity	NPC79943
0.5062	Remote Similarity	NPC290133
0.506	Remote Similarity	NPC227579

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC74924 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4444
0.1-0.2	4667
0.2-0.3	27
0.3-0.4	9
0.4-0.5	1
0.5-0.6	2
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
0.5072	Remote Similarity	NPD1550	Phase 2
0.5072	Remote Similarity	NPD1552	Clinical (unspecified phase)

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