NPASS Compound

Natural Product: NPC259834

Natural Product ID	NPC259834
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phellamurin
IUPAC Name	(2R,3R)-3,5-dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,3-dihydrochromen-4-one
Synonyms	Phellamurin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL516116
PubChem CID	193876
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 67 70 0 0 0 0 0 0 0 0999 V2000 -6.3420 -1.0710 -2.7511 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0137 -1.8739 -1.6638 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3669 -1.0724 -0.5555 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1926 -0.4568 -0.9842 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4752 -0.1344 0.1986 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1541 0.1940 -0.1012 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0676 -0.4971 0.3505 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1053 -1.6063 1.1626 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0360 -2.2574 1.5819 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0074 -3.3676 2.3951 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2529 -1.7769 1.1708 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3446 -0.6545 0.3462 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1903 -0.0231 -0.0579 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2612 1.1735 -0.9357 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0054 2.4358 -0.1983 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9279 3.3709 -0.1854 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2139 3.1822 -0.8948 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6948 4.6433 0.5478 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6050 -0.2229 -0.0324 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8063 -0.4940 0.6450 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7423 -1.6293 1.6131 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5019 -2.4034 1.5684 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4742 -3.6244 1.8694 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9784 -1.2341 2.9392 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9513 -0.6329 -0.3041 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1762 -0.0422 -0.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2126 -0.2035 -1.0144 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0351 -0.9577 -2.1513 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8229 -1.5476 -2.3660 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8046 -1.3793 -1.4474 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0749 -1.1275 -3.0861 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1971 1.0030 0.9004 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5059 1.2708 0.1920 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2795 -0.0081 -0.0150 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.8018 -0.4074 1.2042 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1924 1.9048 -1.0096 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5134 0.6851 2.2222 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1497 -1.4625 -3.1704 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8733 -2.4007 -1.2477 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2716 -2.6334 -1.9867 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1283 -1.7881 0.2636 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6236 -1.0164 0.8453 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0584 -1.9917 1.4916 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3274 -4.2756 2.1464 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2411 1.1720 -1.4221 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5291 1.0794 -1.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9309 2.6006 0.3310 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7715 4.1632 -0.9190 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8942 2.4741 -0.4214 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0482 2.9462 -1.9876 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1341 5.2302 0.0785 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4241 4.4724 1.6026 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5901 5.2761 0.5396 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0070 0.4324 1.2638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5797 -2.3405 1.3473 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9517 -1.1467 3.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3010 0.5525 0.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1564 0.2719 -0.8215 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6560 -2.1493 -3.2571 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8665 -1.8723 -1.6738 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9249 -1.5866 -2.8368 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6006 1.9273 0.9265 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1126 1.9153 0.8581 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0670 0.1610 -0.7778 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6700 -1.3799 1.3676 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9732 2.1762 -1.5261 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8603 0.0350 2.6085 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 9 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 3 16 17 1 0 16 18 1 0 12 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 21 24 1 0 20 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 28 31 1 0 5 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 33 36 1 0 32 37 1 0 34 3 1 0 13 7 1 0 30 25 1 0 22 11 1 0 1 38 1 0 2 39 1 0 2 40 1 0 3 41 1 1 5 42 1 1 8 43 1 0 10 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 17 48 1 0 17 49 1 0 17 50 1 0 18 51 1 0 18 52 1 0 18 53 1 0 20 54 1 1 21 55 1 6 24 56 1 0 26 57 1 0 27 58 1 0 29 59 1 0 30 60 1 0 31 61 1 0 32 62 1 1 33 63 1 1 34 64 1 6 35 65 1 0 36 66 1 0 37 67 1 0 M END

Standard InCHIKey	GRDZTDZJQRPNCN-YIANMRPHSA-N
Standard InCHI	InChI=1S/C26H30O11/c1-11(2)3-8-14-16(35-26-23(34)21(32)19(30)17(10-27)36-26)9-15(29)18-20(31)22(33)24(37-25(14)18)12-4-6-13(28)7-5-12/h3-7,9,17,19,21-24,26-30,32-34H,8,10H2,1-2H3/t17-,19-,21+,22+,23-,24-,26-/m1/s1
SMILES	OC[C@H]1O[C@@H](Oc2cc(O)c3c(c2CC=C(C)C)O[C@@H]([C@H](C3=O)O)c2ccc(cc2)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	518.18	Volume:	499.627 ? Van der Waals volume.
Dense:	1.037	LogP:	1.082 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.991 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.198 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.263	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.506	Fsp³:	0.423
MCE-18:	94.595 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.693	Fluc inhibitor:	0.307 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.363 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.658 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.172	Promiscuous compounds:	0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.413	MDCK Permeability:	-5.129
Pgp-inhibitor:	0.009	Pgp-substrate:	0.376
PAMPA:	0.982 ? 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):	0.1
20% Bioavailability (F20%):	0.449	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.393
Plasma Protein Binding (PPB):	69.84%	Volume Distribution (VD):	-0.01
Fu:	31.435% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.55
BSEP inhibitor:	0.008

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.948
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.923
HLM stability:	0.019 ? 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):

3.329

Half-life (T1/2):

4.124

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.114
Human Hepatotoxicity (H-HT):	0.804	Drug-induced Liver Injury (DILI):	0.854
AMES Toxicity:	0.871	Rat Oral Acute Toxicity:	0.064
Maximum Recommended Daily Dose:	0.06	Skin Sensitization:	0.999
Carcinogencity:	0.042	Eye Corrosion:	0.0
Eye Irritation:	0.019	Respiratory Toxicity:	0.089
Drug-induced Neurotoxicity:	0.023	Ototoxicity:	0.984
Hematotoxicity:	0.343	Drug-induced Nephrotoxicity:	0.931
Genotoxicity:	0.988	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.564	Hek293 Cytotoxicity:	0.588
BCF:	0.977 ? 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:	3.672 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.382 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.561 ? 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
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[14510598]
NPO4513	Commiphora africana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679332]
NPO4513	Commiphora africana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37653941]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4513	Commiphora africana	Species	Burseraceae	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	2
Activity	1

Activity Type	# Activity
Individual protein	1
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1310	Individual protein	Xanthine dehydrogenase	Bos taurus	Inhibition	=	0.0	%	PMID[3379415]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1	Others	Radical scavenging activity	n.a.	Inhibition	=	34.6	%	PMID[14510598]
NPT2	Others	Unspecified	n.a.	Activity	=	62.0	%	PMID[15679332]

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 NPC259834 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	12316
0.1-0.2	30785
0.2-0.3	5485
0.3-0.4	1051
0.4-0.5	195
0.5-0.6	21
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	Natural Product ID
0.5946	Remote Similarity	NPC262038
0.5946	Remote Similarity	NPC319910
0.5875	Remote Similarity	NPC163191
0.5733	Remote Similarity	NPC97326
0.5647	Remote Similarity	NPC23817
0.5556	Remote Similarity	NPC48579
0.5488	Remote Similarity	NPC88484
0.5422	Remote Similarity	NPC39351
0.5366	Remote Similarity	NPC169248
0.5366	Remote Similarity	NPC72649
0.5309	Remote Similarity	NPC177742
0.5256	Remote Similarity	NPC254412
0.5238	Remote Similarity	NPC471457
0.5158	Remote Similarity	NPC168789
0.5125	Remote Similarity	NPC278476
0.5122	Remote Similarity	NPC57587
0.5119	Remote Similarity	NPC328093
0.5119	Remote Similarity	NPC259182
0.5063	Remote Similarity	NPC35567
0.5063	Remote Similarity	NPC477240
0.5057	Remote Similarity	NPC472320

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC259834 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3846
0.1-0.2	5171
0.2-0.3	116
0.3-0.4	15
0.4-0.5	2
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