NPASS Compound

Natural Product: NPC307895

Natural Product ID	NPC307895
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Mammeasin B
IUPAC Name	[(1S)-1-[6-[(2E)-3,7-dimethylocta-2,6-dienyl]-5,7-dihydroxy-8-(3-methylbutanoyl)-2-oxochromen-4-yl]propyl] acetate
Synonyms	Mammeasin B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2064607
PubChem CID	66559531
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

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 74 75 0 0 0 0 0 0 0 0999 V2000 -0.6120 4.4613 1.6504 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4421 3.1910 1.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0030 3.0904 0.1428 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8260 1.8831 -0.0576 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1928 1.8798 0.1722 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0163 0.7986 0.0070 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2643 0.8933 0.2441 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4786 -0.3220 -0.3993 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2139 -0.4249 -0.6417 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3403 0.6603 -0.4838 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0039 0.4897 -0.7571 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1673 1.5578 -0.5969 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5182 -0.7185 -1.1791 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9154 -0.9567 -1.4922 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7665 -1.0753 -0.3223 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8499 -0.3374 -0.1352 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6709 -0.5348 1.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0604 -0.9891 0.8964 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9358 -0.1235 0.0963 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0188 0.4229 0.6742 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3232 0.1497 2.1114 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9074 1.2931 -0.1114 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2274 0.6784 -1.1445 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4121 -1.7874 -1.3290 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7534 -1.6698 -1.0696 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6678 -2.7969 -1.2391 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1904 -2.9208 -2.4000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0280 -3.7737 -0.2160 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2200 -5.0636 -0.3043 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4630 -5.6800 -1.6535 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6667 -6.0185 0.8093 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9226 -2.9913 -1.7507 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9768 4.1746 0.1585 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9708 5.2479 -0.6663 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0443 5.3265 -1.5290 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0044 6.3134 -0.5841 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0058 4.5711 0.7274 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2648 5.3697 1.6835 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0731 4.4474 2.5080 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3208 3.3365 2.2315 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8321 2.3769 1.8923 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3677 3.4207 -0.6618 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6581 2.8126 0.5133 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5847 1.5240 0.0992 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9942 -1.9482 -2.0498 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2438 -0.2234 -2.2642 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5236 -1.7957 0.4484 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6972 0.4639 1.6058 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1378 -1.2446 1.7787 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0935 -2.0461 0.4694 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5433 -1.1375 1.9141 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7870 0.1009 -0.9479 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4683 0.4859 2.7254 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5430 -0.9252 2.2608 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2154 0.7319 2.4259 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7426 2.3616 0.1027 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7123 1.1665 -1.2050 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9968 1.0891 0.0658 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3283 1.2422 -1.5237 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9184 1.4434 -0.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7004 0.2436 -2.0330 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1194 -3.9879 -0.3158 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9086 -3.3825 0.8309 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -4.8551 -0.1623 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5238 -5.8091 -1.8663 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9169 -6.6318 -1.7966 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0403 -4.9573 -2.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5195 -5.5625 1.3539 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0588 -6.9357 0.3279 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8645 -6.2017 1.5225 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3255 -3.5825 -1.1928 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8659 5.9607 -1.1747 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6189 7.2848 -0.9780 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2334 6.4659 0.4917 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 2 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 11 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 3 20 21 1 0 20 22 1 0 16 23 1 0 13 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 24 32 1 0 3 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 10 4 1 0 25 9 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 2 41 1 0 3 42 1 6 5 43 1 0 12 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 17 48 1 0 17 49 1 0 18 50 1 0 18 51 1 0 19 52 1 0 21 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 22 57 1 0 22 58 1 0 23 59 1 0 23 60 1 0 23 61 1 0 28 62 1 0 28 63 1 0 29 64 1 0 30 65 1 0 30 66 1 0 30 67 1 0 31 68 1 0 31 69 1 0 31 70 1 0 32 71 1 0 36 72 1 0 36 73 1 0 36 74 1 0 M END

Standard InCHIKey	ORNWXFDALTWWQH-SJQUQUAPSA-N
Standard InCHI	InChI=1S/C29H38O7/c1-8-23(35-19(7)30)21-15-24(32)36-29-25(21)27(33)20(13-12-18(6)11-9-10-16(2)3)28(34)26(29)22(31)14-17(4)5/h10,12,15,17,23,33-34H,8-9,11,13-14H2,1-7H3/b18-12+/t23-/m0/s1
SMILES	CC[C@@H](c1cc(=O)oc2c1c(O)c(C/C=C(/CCC=C(C)C)C)c(c2C(=O)CC(C)C)O)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	498.26	Volume:	530.831 ? Van der Waals volume.
Dense:	0.939	LogP:	6.061 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.238 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.654 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	16.0
TPSA:	114.04 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.154	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.826	Fsp³:	0.483
MCE-18:	40.0 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.963	Fluc inhibitor:	0.033 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.924 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.899 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.199	Promiscuous compounds:	0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.844	MDCK Permeability:	-4.634
Pgp-inhibitor:	0.999	Pgp-substrate:	0.003
PAMPA:	0.01 ? 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%):	0.456	30% Bioavailability (F30%):	0.738
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.994
Plasma Protein Binding (PPB):	97.077%	Volume Distribution (VD):	0.072
Fu:	2.584% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.025
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.978	CYP2C19-substrate:	0.92
CYP2C9-inhibitor:	0.185	CYP2C9-substrate:	0.168
CYP2D6-inhibitor:	0.043	CYP2D6-substrate:	0.132
CYP3A4-inhibitor:	0.019	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

2.386

Half-life (T1/2):

0.958

ADMET: Toxicity

hERG Blockers:	0.057	hERG Blockers (10um):	0.286
Human Hepatotoxicity (H-HT):	0.845	Drug-induced Liver Injury (DILI):	0.94
AMES Toxicity:	0.211	Rat Oral Acute Toxicity:	0.565
Maximum Recommended Daily Dose:	0.703	Skin Sensitization:	0.97
Carcinogencity:	0.328	Eye Corrosion:	0.001
Eye Irritation:	0.687	Respiratory Toxicity:	0.796
Drug-induced Neurotoxicity:	0.271	Ototoxicity:	0.388
Hematotoxicity:	0.626	Drug-induced Nephrotoxicity:	0.797
Genotoxicity:	0.98	RPMI-8226 Immunitoxicity:	0.237
A549 Cytotoxicity:	0.525	Hek293 Cytotoxicity:	0.227
BCF:	1.784 ? 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:	5.11 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.781 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.464 ? 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
NPO32974	mammea siamensis	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22831798]
NPO32974	mammea siamensis	Species	Calophyllaceae	Eukaryota	flower	n.a.	n.a.	PMID[23206866]

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	4
Activity	3
IC50	1

Activity Type	# Activity
Cell line	8

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
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	0.6	%	PMID[15332839]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	31.1	%	PMID[25695368]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	64.7	%	PMID[26890116]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	88.2	%	PMID[20100877]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	60.3	%	PMID[2869146]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	20.2	%	PMID[20163893]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	13.6	%	PMID[25237727]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	6400.0	nM	PMID[20070106]

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 NPC307895 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	7689
0.1-0.2	39480
0.2-0.3	2432
0.3-0.4	224
0.4-0.5	16
0.5-0.6	4
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8767	High Similarity	NPC112829
0.8514	High Similarity	NPC470553
0.7273	Intermediate Similarity	NPC118059
0.72	Intermediate Similarity	NPC470556
0.6296	Remote Similarity	NPC33653
0.6104	Remote Similarity	NPC183639
0.6098	Remote Similarity	NPC470554
0.6076	Remote Similarity	NPC19476
0.6	Remote Similarity	NPC181388
0.5854	Remote Similarity	NPC288910
0.5542	Remote Similarity	NPC483432
0.506	Remote Similarity	NPC470909
0.5056	Remote Similarity	NPC178627

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC307895 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2180
0.1-0.2	6901
0.2-0.3	69
0.3-0.4	0
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