NPASS Compound

Natural Product: NPC470828

Natural Product ID	NPC470828
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5''-Methoxy-4''-O-(8-Guaiacylglycerol)Buddlenol A
IUPAC Name	(E)-3-[(2R,3S)-2-[4-[1-[4-[1,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-1,3-dihydroxypropan-2-yl]oxy-3,5-dimethoxyphenyl]-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]prop-2-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL225532
PubChem CID	16216401
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 106110 0 0 0 0 0 0 0 0999 V2000 -7.7678 3.7779 -2.9623 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0422 2.7281 -2.3352 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6628 1.9301 -1.3492 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9737 2.1633 -0.9911 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6045 1.4114 -0.0372 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7904 0.4009 0.5240 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4933 0.1687 0.1713 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8987 0.9425 -0.7887 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5742 0.5138 -0.9820 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5144 -0.8277 -0.5140 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4692 -0.8056 0.6408 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8482 -0.2479 1.9072 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2628 0.9747 1.6355 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1668 -1.3075 -0.2264 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9531 -2.6675 -0.1275 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6502 -3.1319 0.1152 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5755 -2.2801 0.2583 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8066 -0.9209 0.1546 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1017 -0.4484 -0.0860 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7125 -0.0882 0.2897 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8834 1.3050 0.1546 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3230 -2.7737 0.4904 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2107 -3.2328 1.6818 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5349 -4.7321 1.6818 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3866 -5.0958 0.6775 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1581 -2.3996 2.4438 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2818 -1.7667 1.7638 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3403 -2.3990 1.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4043 -1.7078 0.5776 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4262 -0.3316 0.5528 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3632 0.3307 1.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3218 -0.3538 1.7295 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4223 1.7209 1.1095 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4626 2.5312 1.6921 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4685 0.3690 -0.0414 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6565 0.7386 0.6165 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6886 2.2310 0.9077 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5468 3.0088 -0.2173 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8822 0.2144 -0.0306 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0006 0.7000 -1.4315 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6484 1.8970 -1.6363 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7811 2.4267 -2.9134 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2669 1.7623 -4.0022 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6243 0.5686 -3.7835 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4865 0.0342 -2.5206 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3941 2.2814 -5.2787 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4280 3.6185 -3.0902 O 0 0 0 0 0 0 0 0 0 0 0 0 9.9842 4.3668 -2.0522 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0447 0.5664 0.6472 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4662 -2.4009 -0.0087 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4841 -3.8287 -0.0021 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5661 -3.2070 3.5501 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4510 -4.5001 0.2125 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5284 -5.3975 0.0764 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9541 1.5807 0.4449 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.8838 2.4228 0.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1184 3.6327 -0.3921 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3698 4.2758 -1.1263 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0780 4.3286 -3.6283 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2095 4.4654 -2.2028 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5318 3.2979 -3.6052 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4949 2.9377 -1.4941 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2525 -0.2271 1.2916 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0127 -1.4314 -1.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9059 -1.8032 0.8611 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6703 -0.1185 2.6280 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1033 -0.9401 2.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7661 1.7363 1.9753 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7418 -3.3992 -0.2285 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2234 0.6318 -0.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0740 1.8035 -0.1497 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3089 1.7569 1.0662 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6008 1.5604 -0.6810 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7402 -3.2465 2.3912 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3820 -5.3509 1.7110 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9897 -4.8935 2.7062 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0042 -5.8738 0.1788 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5240 -1.6063 2.9770 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3851 -3.4736 1.1823 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4972 0.1626 2.1878 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6857 2.7222 2.7819 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4608 2.0813 1.6824 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4631 3.5520 1.2370 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6237 0.2732 1.6545 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7004 2.4082 1.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9738 2.4582 1.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8788 2.5589 -0.7985 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8354 -0.9012 -0.0040 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0934 2.4648 -0.8140 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1993 0.0046 -4.6304 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9783 -0.9148 -2.3366 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3797 3.3128 -5.3349 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6124 3.6720 -1.4433 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2009 4.8341 -1.3946 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5808 5.1946 -2.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9619 0.4687 1.6334 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5189 -4.2300 -0.3680 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6636 -4.2178 1.0055 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2772 -4.2167 -0.6624 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8968 -2.6317 4.2873 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3023 -5.1089 0.8476 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0464 -5.2763 -0.9061 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1914 -6.4432 0.2109 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2541 0.6926 1.1397 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8353 2.0988 0.9267 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.1579 4.0842 -0.2496 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 10 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 17 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 23 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 30 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 36 39 1 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 43 46 1 0 42 47 1 0 47 48 1 0 39 49 1 0 29 50 1 0 50 51 1 0 26 52 1 0 16 53 1 0 53 54 1 0 5 55 1 0 55 56 2 3 56 57 1 0 57 58 2 0 8 3 1 0 11 7 1 0 19 14 1 0 32 27 1 0 45 40 1 0 1 59 1 0 1 60 1 0 1 61 1 0 4 62 1 0 6 63 1 0 10 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 0 15 69 1 0 19 70 1 0 21 71 1 0 21 72 1 0 21 73 1 0 23 74 1 0 24 75 1 0 24 76 1 0 25 77 1 0 26 78 1 0 28 79 1 0 32 80 1 0 34 81 1 0 34 82 1 0 34 83 1 0 36 84 1 0 37 85 1 0 37 86 1 0 38 87 1 0 39 88 1 0 41 89 1 0 44 90 1 0 45 91 1 0 46 92 1 0 48 93 1 0 48 94 1 0 48 95 1 0 49 96 1 0 51 97 1 0 51 98 1 0 51 99 1 0 52100 1 0 54101 1 0 54102 1 0 54103 1 0 55104 1 0 56105 1 0 57106 1 0 M END

Standard InCHIKey	ZCFXYUOLSAFDRL-ZXJVSXSISA-N
Standard InCHI	InChI=1S/C42H48O16/c1-50-29-14-23(9-10-28(29)47)37(48)35(20-45)56-41-31(52-3)15-24(16-32(41)53-4)38(49)36(21-46)57-42-33(54-5)17-25(18-34(42)55-6)39-27(19-44)26-12-22(8-7-11-43)13-30(51-2)40(26)58-39/h7-18,27,35-39,44-49H,19-21H2,1-6H3/b8-7+/t27-,35?,36?,37?,38?,39+/m1/s1
SMILES	COC1=CC(=CC2=C1OC(C2CO)C3=CC(=C(C(=C3)OC)OC(CO)C(C4=CC(=C(C(=C4)OC)OC(CO)C(C5=CC(=C(C=C5)O)OC)O)OC)O)OC)C=CC=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	808.29	Volume:	795.939 ? Van der Waals volume.
Dense:	1.016	LogP:	1.615 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.064 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.928 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	20.0	Rigid Bonds:	30.0
TPSA:	221.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.055	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.998	Fsp³:	0.357
MCE-18:	110.526 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.42	Fluc inhibitor:	0.237 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.129 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.394 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.287	Promiscuous compounds:	0.036

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.001	MDCK Permeability:	-4.829
Pgp-inhibitor:	0.001	Pgp-substrate:	0.004
PAMPA:	0.183 ? 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):	0.006
20% Bioavailability (F20%):	0.061	30% Bioavailability (F30%):	0.235
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.925
Plasma Protein Binding (PPB):	78.748%	Volume Distribution (VD):	-0.173
Fu:	22.022% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.802
BSEP inhibitor:	0.834

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.698	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.7	CYP2C9-substrate:	0.077
CYP2D6-inhibitor:	0.992	CYP2D6-substrate:	0.854
CYP3A4-inhibitor:	0.304	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.091 ? 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):

5.536

Half-life (T1/2):

2.814

ADMET: Toxicity

hERG Blockers:	0.104	hERG Blockers (10um):	0.299
Human Hepatotoxicity (H-HT):	0.657	Drug-induced Liver Injury (DILI):	0.073
AMES Toxicity:	0.349	Rat Oral Acute Toxicity:	0.049
Maximum Recommended Daily Dose:	0.722	Skin Sensitization:	0.778
Carcinogencity:	0.275	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.074
Drug-induced Neurotoxicity:	0.649	Ototoxicity:	0.999
Hematotoxicity:	0.045	Drug-induced Nephrotoxicity:	0.968
Genotoxicity:	0.044	RPMI-8226 Immunitoxicity:	0.413
A549 Cytotoxicity:	0.169	Hek293 Cytotoxicity:	0.549
BCF:	0.77 ? 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:	3.514 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.39 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.315 ? 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
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16792422]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17343407]
NPO14922	Tarenna attenuata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14922	Tarenna attenuata	Species	Rubiaceae	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
Activity	4
IC50	1

Activity Type	# Activity
Cell line	4
Others	1

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
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	50.3	%	PMID[23186727]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	54.7	%	PMID[20000781]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	55.2	%	PubChem BioAssay data set
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	51.0	%	PubChem BioAssay data set
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	127000.0	nM	PMID[18183025]

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 NPC470828 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	24958
0.1-0.2	22091
0.2-0.3	2509
0.3-0.4	191
0.4-0.5	61
0.5-0.6	31
0.6-0.7	8
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9718	High Similarity	NPC470769
0.9211	High Similarity	NPC470827
0.84	Intermediate Similarity	NPC260397
0.7403	Intermediate Similarity	NPC43065
0.6986	Remote Similarity	NPC284881
0.6986	Remote Similarity	NPC93433
0.6986	Remote Similarity	NPC474444
0.6944	Remote Similarity	NPC267291
0.6421	Remote Similarity	NPC485396
0.6421	Remote Similarity	NPC485394
0.6421	Remote Similarity	NPC485395
0.6267	Remote Similarity	NPC473408
0.5974	Remote Similarity	NPC476387
0.5974	Remote Similarity	NPC237594
0.5974	Remote Similarity	NPC119060
0.5844	Remote Similarity	NPC156502
0.5844	Remote Similarity	NPC10737
0.5789	Remote Similarity	NPC7903
0.5789	Remote Similarity	NPC160991
0.5765	Remote Similarity	NPC181615
0.575	Remote Similarity	NPC206413
0.575	Remote Similarity	NPC482649
0.575	Remote Similarity	NPC149003
0.575	Remote Similarity	NPC482647
0.575	Remote Similarity	NPC482648
0.575	Remote Similarity	NPC482651
0.575	Remote Similarity	NPC194244
0.575	Remote Similarity	NPC482650
0.5556	Remote Similarity	NPC253878
0.5556	Remote Similarity	NPC471414
0.5422	Remote Similarity	NPC163898
0.5309	Remote Similarity	NPC224876
0.5256	Remote Similarity	NPC87725
0.5256	Remote Similarity	NPC263261
0.5176	Remote Similarity	NPC480707
0.5063	Remote Similarity	NPC300757
0.5062	Remote Similarity	NPC147821
0.5062	Remote Similarity	NPC319625
0.5062	Remote Similarity	NPC183181
0.5062	Remote Similarity	NPC41706
0.506	Remote Similarity	NPC470098
0.506	Remote Similarity	NPC473266
0.5059	Remote Similarity	NPC470097

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470828 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4337
0.1-0.2	4733
0.2-0.3	76
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