NPASS Compound

Natural Product: NPC475260

Natural Product ID	NPC475260
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isoannonacin
IUPAC Name	5-[(11S)-6,11-dihydroxy-11-[(2S,5S)-5-[(1S)-1-hydroxytridecyl]oxolan-2-yl]undecyl]-3-(2-oxopropyl)oxolan-2-one
Synonyms	Isoannonacin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL502181
PubChem CID	44584481
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 106107 0 0 0 0 0 0 0 0999 V2000 8.4922 4.1613 1.4232 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3255 3.2708 2.6290 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4116 2.2616 2.7667 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4887 1.3160 1.5717 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2261 0.5370 1.3691 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3828 -0.4123 0.2139 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6672 0.3176 -1.0569 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8713 -0.5281 -2.2345 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9930 -1.5278 -2.7573 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6440 -1.4821 -3.2689 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4417 -1.1732 -2.4895 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1464 0.1149 -1.8794 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8263 0.2303 -1.1604 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4728 -0.5062 0.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5374 -1.9271 0.2640 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1327 -2.3640 -0.2212 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3450 -1.2343 0.4516 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0991 -0.1316 0.2982 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0128 -1.1520 -0.1485 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9056 -0.1791 0.5570 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0669 -0.5554 1.9835 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0285 0.3239 2.7423 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4366 0.2485 2.1168 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9354 -1.1410 2.1414 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2414 -1.5242 1.6474 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7030 -1.3630 0.2692 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8114 0.0122 -0.2736 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3871 -0.0320 -1.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7408 -0.6560 -1.7574 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7697 0.0508 -0.9221 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9956 1.4802 -1.3471 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5128 1.6524 -1.1892 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0526 0.2764 -1.2643 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2319 -0.0318 -1.5562 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0237 -0.5963 -0.9555 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.8301 2.3050 0.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2809 2.4897 0.3322 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.0189 1.5330 0.4129 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.8419 3.8714 0.4312 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8638 -1.6272 3.4958 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0173 -0.9345 -1.5307 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8920 -0.0622 -2.2423 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5641 4.3164 1.1647 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0344 5.1580 1.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9582 3.7712 0.5450 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3473 3.9079 3.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3214 2.8095 2.5541 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3908 2.8051 2.7684 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2748 1.6668 3.6705 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7070 1.9588 0.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3368 0.6222 1.6981 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9452 -0.0417 2.2967 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3430 1.1880 1.1847 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1501 -1.1672 0.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4109 -0.9727 0.1230 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7214 0.8312 -0.9138 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0224 1.1720 -1.2027 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8880 -1.0735 -2.0361 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1184 0.1936 -3.1014 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6324 -2.0710 -3.6039 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0340 -2.4829 -2.0226 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6157 -0.8279 -4.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4214 -2.5091 -3.8089 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5329 -1.3464 -3.2242 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3281 -2.0527 -1.7794 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9446 0.5926 -1.2654 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0407 0.8687 -2.7322 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6399 1.3232 -1.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9712 -0.0056 0.9470 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3076 -2.5830 -0.0248 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4275 -2.1331 1.4104 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8812 -3.3508 0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0918 -2.2445 -1.3028 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2040 -1.5225 1.5281 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4882 -2.1691 0.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8652 -0.0321 0.0177 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3978 0.8283 0.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2137 -1.6376 2.1432 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0614 -0.3320 2.4703 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1173 -0.0026 3.7737 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7239 1.3671 2.6884 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4088 0.7410 1.1333 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0686 0.8787 2.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1713 -1.8484 1.6351 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4300 -2.6148 2.0066 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0319 -1.0013 2.3251 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7691 -1.7834 0.2429 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1853 -2.0603 -0.4567 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8644 0.5602 -0.4343 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5180 0.6281 0.3099 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4312 0.9907 -2.1451 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6956 -0.6612 -2.2935 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7330 -1.7360 -1.5313 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0724 -0.6028 -2.8332 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4419 0.0702 0.1447 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6637 1.6766 -2.3668 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4535 2.1902 -0.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8675 2.2865 -2.0266 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2616 3.2465 0.2315 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4216 1.5975 0.9138 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.9397 3.8942 0.2876 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.3995 4.4582 -0.3950 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5773 4.3808 1.3654 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7878 -2.6037 3.5080 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3358 -0.0438 -1.7809 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0686 0.5313 -2.9954 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 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 32 36 1 0 36 37 1 0 37 38 2 0 37 39 1 0 24 40 1 0 19 41 1 0 13 42 1 0 18 14 1 0 35 30 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 0 2 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 5 52 1 0 5 53 1 0 6 54 1 0 6 55 1 0 7 56 1 0 7 57 1 0 8 58 1 0 8 59 1 0 9 60 1 0 9 61 1 0 10 62 1 0 10 63 1 0 11 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 0 14 69 1 0 15 70 1 0 15 71 1 0 16 72 1 0 16 73 1 0 17 74 1 0 19 75 1 0 20 76 1 0 20 77 1 0 21 78 1 0 21 79 1 0 22 80 1 0 22 81 1 0 23 82 1 0 23 83 1 0 24 84 1 0 25 85 1 0 25 86 1 0 26 87 1 0 26 88 1 0 27 89 1 0 27 90 1 0 28 91 1 0 28 92 1 0 29 93 1 0 29 94 1 0 30 95 1 0 31 96 1 0 31 97 1 0 32 98 1 0 36 99 1 0 36100 1 0 39101 1 0 39102 1 0 39103 1 0 40104 1 0 41105 1 0 42106 1 0 M END

Standard InCHIKey	DGQPZGGOYKKJLX-LVBQAKHDSA-N
Standard InCHI	InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(37)18-13-12-14-20-30-26-28(25-27(2)36)35(40)41-30/h28-34,37-39H,3-26H2,1-2H3/t28?,29?,30?,31-,32-,33-,34-/m0/s1
SMILES	CCCCCCCCCCCCC(C1CCC(O1)C(CCCCC(CCCCCC2CC(C(=O)O2)CC(=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	596.47	Volume:	653.062 ? Van der Waals volume.
Dense:	0.913	LogP:	6.126 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.12 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.596 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	12.0
TPSA:	113.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.071	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.565	Fsp³:	0.943
MCE-18:	33.088 ? 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:	0.626	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.046 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.393	Promiscuous compounds:	0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.258	MDCK Permeability:	-4.836
Pgp-inhibitor:	0.002	Pgp-substrate:	0.141
PAMPA:	0.059 ? 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):	0.996
20% Bioavailability (F20%):	0.94	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.819

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.992
Plasma Protein Binding (PPB):	92.906%	Volume Distribution (VD):	0.487
Fu:	5.5% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.101
BSEP inhibitor:	0.554

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.308	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.478	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.338	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.174
HLM stability:	0.044 ? 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):

5.516

Half-life (T1/2):

1.062

ADMET: Toxicity

hERG Blockers:	0.471	hERG Blockers (10um):	0.747
Human Hepatotoxicity (H-HT):	0.567	Drug-induced Liver Injury (DILI):	0.096
AMES Toxicity:	0.012	Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.339	Skin Sensitization:	0.999
Carcinogencity:	0.021	Eye Corrosion:	0.002
Eye Irritation:	0.38	Respiratory Toxicity:	0.493
Drug-induced Neurotoxicity:	0.017	Ototoxicity:	0.929
Hematotoxicity:	0.038	Drug-induced Nephrotoxicity:	0.704
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.026
A549 Cytotoxicity:	0.057	Hek293 Cytotoxicity:	0.044
BCF:	0.953 ? 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:	5.057 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.354 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.689 ? 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
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1021/np50053a043]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8277309]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	Bark	n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9632	Annona reticulata	Species	Annonaceae	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
ED50	9

Activity Type	# Activity
Cell line	7
Non-molecular	2

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
NPT81	Cell line	A549	Homo sapiens	ED50	=	2.0	10'-2 ug/ml	PMID[12166949]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	2.0	10'-3 ug/ml	DrugMatrix in vitro pharmacology data
NPT168	Cell line	P388	Mus musculus	ED50	=	3.0	ug ml-1	PMID[24164206]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	3.0	ug ml-1	PMID[2189947]

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 NPC475260 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	16396
0.1-0.2	30372
0.2-0.3	2751
0.3-0.4	115
0.4-0.5	124
0.5-0.6	73
0.6-0.7	1
0.7-0.8	0
0.8-0.85	6
0.85-0.9	3
0.9-0.95	2
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC482767
1.0	High Similarity	NPC488621
1.0	High Similarity	NPC473775
1.0	High Similarity	NPC488622
0.9556	High Similarity	NPC480251
0.9556	High Similarity	NPC480250
0.9302	High Similarity	NPC474100
0.9302	High Similarity	NPC475232
0.875	High Similarity	NPC480076
0.875	High Similarity	NPC480077
0.8511	High Similarity	NPC475616
0.8478	Intermediate Similarity	NPC488234
0.8333	Intermediate Similarity	NPC473699
0.8333	Intermediate Similarity	NPC51249
0.8298	Intermediate Similarity	NPC480078
0.8298	Intermediate Similarity	NPC480071
0.8163	Intermediate Similarity	NPC480075
0.7273	Intermediate Similarity	NPC475206
0.7091	Intermediate Similarity	NPC473791
0.6078	Remote Similarity	NPC480072
0.5686	Remote Similarity	NPC480074
0.566	Remote Similarity	NPC107986
0.566	Remote Similarity	NPC223871
0.566	Remote Similarity	NPC231009
0.566	Remote Similarity	NPC103284
0.566	Remote Similarity	NPC110710
0.566	Remote Similarity	NPC1083
0.566	Remote Similarity	NPC82795
0.566	Remote Similarity	NPC286338
0.566	Remote Similarity	NPC603931
0.566	Remote Similarity	NPC604237
0.5614	Remote Similarity	NPC20621
0.5614	Remote Similarity	NPC318963
0.5614	Remote Similarity	NPC605101
0.5556	Remote Similarity	NPC488253
0.5556	Remote Similarity	NPC473669
0.5556	Remote Similarity	NPC488251
0.5472	Remote Similarity	NPC606043
0.5455	Remote Similarity	NPC232555
0.5455	Remote Similarity	NPC171174
0.5455	Remote Similarity	NPC182383
0.5455	Remote Similarity	NPC114694
0.5455	Remote Similarity	NPC485248
0.5455	Remote Similarity	NPC142117
0.5455	Remote Similarity	NPC480249
0.5455	Remote Similarity	NPC485249
0.5455	Remote Similarity	NPC240695
0.5424	Remote Similarity	NPC258068
0.5424	Remote Similarity	NPC476583
0.537	Remote Similarity	NPC100921
0.537	Remote Similarity	NPC475159
0.537	Remote Similarity	NPC131002
0.537	Remote Similarity	NPC473780
0.537	Remote Similarity	NPC477018
0.537	Remote Similarity	NPC604521
0.5357	Remote Similarity	NPC488632
0.5357	Remote Similarity	NPC477011
0.5333	Remote Similarity	NPC477014
0.5333	Remote Similarity	NPC477013
0.5254	Remote Similarity	NPC473478
0.5254	Remote Similarity	NPC473651
0.5254	Remote Similarity	NPC139418
0.5254	Remote Similarity	NPC66346
0.5179	Remote Similarity	NPC156804
0.5172	Remote Similarity	NPC178215
0.5172	Remote Similarity	NPC473687
0.5172	Remote Similarity	NPC204686
0.5172	Remote Similarity	NPC219498
0.5172	Remote Similarity	NPC308412
0.5172	Remote Similarity	NPC134885
0.5172	Remote Similarity	NPC488247
0.5172	Remote Similarity	NPC210218
0.5172	Remote Similarity	NPC488248
0.5167	Remote Similarity	NPC283085
0.5167	Remote Similarity	NPC169511
0.5167	Remote Similarity	NPC287164
0.5167	Remote Similarity	NPC234077
0.5161	Remote Similarity	NPC488630
0.5161	Remote Similarity	NPC488625
0.5161	Remote Similarity	NPC488626
0.5088	Remote Similarity	NPC93794
0.5088	Remote Similarity	NPC134865
0.5088	Remote Similarity	NPC473504
0.5088	Remote Similarity	NPC103523
0.5088	Remote Similarity	NPC81778
0.5088	Remote Similarity	NPC40066
0.5088	Remote Similarity	NPC488627
0.5088	Remote Similarity	NPC47937
0.5088	Remote Similarity	NPC488631
0.5085	Remote Similarity	NPC488250
0.5085	Remote Similarity	NPC477010
0.5077	Remote Similarity	NPC477017
0.5077	Remote Similarity	NPC477016

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475260 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6004
0.1-0.2	3053
0.2-0.3	92
0.3-0.4	1
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