NPASS Compound

Natural Product: NPC54230

Natural Product ID	NPC54230
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MDFCJNFOINXVSU-CULIVVSNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71571448
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003788] Aconitane-type diterpenoid alkaloids

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 84 90 0 0 0 0 0 0 0 0999 V2000 -2.6469 3.5158 -0.3126 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4473 2.1457 -0.0750 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.5301 1.3753 0.3842 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1921 -0.0103 0.8404 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0426 0.1574 2.4046 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1233 1.2867 2.6391 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7553 0.8368 2.1056 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7774 0.4826 0.6835 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5914 0.0188 0.3129 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6541 1.0481 0.5480 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5491 1.0841 -0.7030 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3672 -0.3090 -1.1981 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8311 -0.3959 -1.0821 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1944 0.4892 -2.0964 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1923 0.8253 -1.5785 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8234 -0.5080 -1.1681 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8798 -0.5103 0.3310 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0103 -0.6166 -1.8021 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0743 -1.6152 -2.7689 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1802 1.5794 -0.2650 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9517 1.6795 -2.5411 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0559 2.1292 -1.6392 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1770 2.5520 -2.3931 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5161 3.8562 -2.1537 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0339 2.7535 -2.6360 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0113 -0.3113 -3.2380 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8947 -1.1945 -0.2293 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7549 -2.2253 -0.4944 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1044 -2.4003 -1.6907 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2845 -3.1257 0.5294 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1482 -4.1458 0.1942 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6576 -5.0084 1.1640 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3163 -4.8725 2.4917 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4527 -3.8533 2.8304 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9455 -2.9929 1.8586 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8805 1.2957 -0.3367 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1186 1.7519 2.5790 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8536 1.2632 3.6877 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3539 -0.9622 0.7999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9808 -1.1585 -0.3904 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0300 -2.0355 -0.3626 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6732 4.0521 -0.2124 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1335 3.7662 -1.2767 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2906 3.9294 0.5184 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0890 1.9293 1.1607 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2631 1.2579 -0.4686 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0620 0.4620 2.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6759 -0.7680 2.8395 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4329 2.2622 2.2888 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9672 1.3757 3.7487 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5969 -0.1204 2.6952 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7973 -0.8846 0.9626 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3382 0.7002 1.3631 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3360 2.0719 0.6795 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7000 -0.5030 -2.2127 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6501 -1.4867 -1.2104 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7670 1.3240 -2.3633 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1945 -1.3566 -1.5884 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6699 -1.5089 0.7675 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8880 -2.6217 -2.4084 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5177 -1.3042 -3.6727 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1569 -1.6165 -3.1043 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4316 2.3808 -0.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3746 1.5758 -3.5624 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7626 3.0187 -1.0444 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3971 4.0883 -2.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8220 4.0594 -1.1088 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7129 4.5633 -2.4911 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2675 2.8816 -3.5702 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8357 -0.5543 -3.6782 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4261 -4.2660 -0.8438 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3368 -5.8155 0.9223 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7160 -5.5490 3.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1899 -3.7537 3.8757 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2691 -2.1948 2.1240 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4282 0.9211 -1.0680 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0779 1.0231 4.4754 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5036 2.0305 4.1152 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3389 0.2985 3.4843 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1760 -0.6181 1.5116 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0676 -1.9485 1.2992 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5160 -2.1723 -1.3422 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8110 -1.7697 0.3862 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6466 -3.0345 -0.0532 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 16 18 1 0 18 19 1 0 15 20 1 0 14 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 21 25 1 0 14 26 1 6 12 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 11 36 1 0 7 37 1 0 37 38 1 0 4 39 1 1 39 40 1 0 40 41 1 0 20 2 1 0 35 30 1 0 17 4 1 0 8 17 1 1 20 8 1 0 13 9 1 0 22 11 1 0 1 42 1 0 1 43 1 0 1 44 1 0 3 45 1 0 3 46 1 0 5 47 1 0 5 48 1 0 6 49 1 0 6 50 1 0 7 51 1 1 9 52 1 1 10 53 1 0 10 54 1 0 12 55 1 0 13 56 1 1 15 57 1 6 16 58 1 1 17 59 1 0 19 60 1 0 19 61 1 0 19 62 1 0 20 63 1 0 21 64 1 6 22 65 1 1 24 66 1 0 24 67 1 0 24 68 1 0 25 69 1 0 26 70 1 0 31 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 35 75 1 0 36 76 1 0 38 77 1 0 38 78 1 0 38 79 1 0 39 80 1 0 39 81 1 0 41 82 1 0 41 83 1 0 41 84 1 0 M END

Standard InCHIKey	MDFCJNFOINXVSU-CULIVVSNSA-N
Standard InCHI	InChI=1S/C31H43NO9/c1-32-14-28(15-37-2)12-11-18(38-3)30-17-13-29(35)25(41-27(34)16-9-7-6-8-10-16)19(17)31(36,24(33)26(29)40-5)20(23(30)32)21(39-4)22(28)30/h6-10,17-26,33,35-36H,11-15H2,1-5H3/t17-,18+,19-,20+,21+,22?,23?,24+,25?,26+,28+,29?,30+,31-/m1/s1
SMILES	CN1C[C@@]2(CC[C@@H]([C@@]34[C@@H]5CC6(C([C@@H]5[C@@]([C@@H]([C@@H](C23)OC)C14)([C@H]([C@@H]6OC)O)O)OC(=O)c1ccccc1)O)OC)COC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	573.29	Volume:	564.4 ? Van der Waals volume.
Dense:	1.016	LogP:	2.102 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.366 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.42 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	31.0
TPSA:	127.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.402	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.16	Fsp³:	0.774
MCE-18:	214.109 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.108	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.352

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.325	MDCK Permeability:	-5.034
Pgp-inhibitor:	0.0	Pgp-substrate:	0.491
PAMPA:	0.95 ? 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%):	0.548	30% Bioavailability (F30%):	0.411
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.776	MRP1:	0.999
Plasma Protein Binding (PPB):	65.45%	Volume Distribution (VD):	0.012
Fu:	37.25% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.978
OATP1B3 inhibitor:	0.816	BCRP inhibitor:	0.001
BSEP inhibitor:	0.071

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.911	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.009
CYP3A4-inhibitor:	0.476	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.091
HLM stability:	0.786 ? 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):

5.785

Half-life (T1/2):

2.162

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.612
Human Hepatotoxicity (H-HT):	0.164	Drug-induced Liver Injury (DILI):	0.178
AMES Toxicity:	0.498	Rat Oral Acute Toxicity:	0.236
Maximum Recommended Daily Dose:	0.255	Skin Sensitization:	0.895
Carcinogencity:	0.275	Eye Corrosion:	0.0
Eye Irritation:	0.014	Respiratory Toxicity:	0.29
Drug-induced Neurotoxicity:	0.268	Ototoxicity:	0.951
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.54
Genotoxicity:	0.037	RPMI-8226 Immunitoxicity:	0.087
A549 Cytotoxicity:	0.11	Hek293 Cytotoxicity:	0.641
BCF:	0.528 ? 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:	3.116 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.378 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.694 ? 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
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	tuber	n.a.	PMID[12913245]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1293938]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16181762]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	roots	n.a.	n.a.	PMID[18044843]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[22223386]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	Lateral roots	n.a.	n.a.	PMID[22607495]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[22628040]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[22907155]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[23225552]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23707213]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[23707213]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24170571]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[24170571]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24190290]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[24190290]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24793215]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	PMID[27761113]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Europe PMC[300080]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	root	n.a.	Europe PMC[300080]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30892884]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4902	Aconitum carmichaelii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14688	Aconitum triphyllum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4893	Aconitum ciliare	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7490	Aconitum japonicum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8847	Aconitum kusnezoffii	Species	Ranunculaceae	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

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

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 NPC54230 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	16547
0.1-0.2	31957
0.2-0.3	1270
0.3-0.4	55
0.4-0.5	13
0.5-0.6	10
0.6-0.7	6
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
0.7126	Intermediate Similarity	NPC124690
0.6818	Remote Similarity	NPC478534
0.6667	Remote Similarity	NPC488604
0.6667	Remote Similarity	NPC281470
0.6264	Remote Similarity	NPC478541
0.6129	Remote Similarity	NPC40539
0.6064	Remote Similarity	NPC172769
0.5876	Remote Similarity	NPC478537
0.5532	Remote Similarity	NPC166521
0.5532	Remote Similarity	NPC478545
0.5417	Remote Similarity	NPC488583
0.5417	Remote Similarity	NPC478535
0.5347	Remote Similarity	NPC476496
0.5306	Remote Similarity	NPC184195
0.5306	Remote Similarity	NPC205
0.5149	Remote Similarity	NPC478539
0.5051	Remote Similarity	NPC478540

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC54230 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3489
0.1-0.2	5530
0.2-0.3	129
0.3-0.4	1
0.4-0.5	1
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